Ilovepdf Merged Compressed

Received: 9 December 2017 | Revised: 11 March 2018 | Accepted: 12 March 2018
DOI: 10.1111/jcpe.12940
2017 WORLD WORKSHOP
Periodontal health and gingival diseases and conditions on

an intact and a reduced periodontium: Consensus report
of workgroup 1 of the 2017 World Workshop on the
Classification of Periodontal and Peri‐Implant Diseases and
Conditions
Iain L.C. Chapple1 | Brian L. Mealey2 | Thomas E. Van Dyke3 | P. Mark Bartold4 |
Henrik Dommisch5 | Peter Eickholz6 | Maria L. Geisinger7 | Robert J. Genco8 |
Michael Glogauer9 | Moshe Goldstein10 | Terrence J. Griffin11 | Palle Holmstrup12 |
Georgia K. Johnson13 | Yvonne Kapila14 | Niklaus P. Lang15 | Joerg Meyle16 |
Shinya Murakami17 | Jacqueline Plemons18 | Giuseppe A. Romito19 | Lior Shapira10 |
Dimitris N. Tatakis20 | Wim Teughels21 | Leonardo Trombelli22 | Clemens Walter23 |
Gernot Wimmer24 | Pinelopi Xenoudi25 | Hiromasa Yoshie26
1
Periodontal Research Group, Institute of Clinical Sciences, College of Medical & Dental Sciences, University of Birmingham, UK
2
University of Texas Health Science Center at San Antonio, USA
3
The Forsyth Institute, Cambridge, MA, USA
4
School of Dentistry, University of Adelaide, Australia
5
Department of Periodontology and Synoptic Dentistry, Charité - Universitätsmedizin Berlin, Germany
6
Department of Periodontology, Center for Oral Medicine, Johann Wolfgang Goethe‐University Frankfurt, Germany
7
Department of Periodontology, University of Alabama at Birmingham, USA
8
Department of Oral Biology, SUNY at Buffalo, NY, USA
9
Faculty of Dentistry, University of Toronto, Canada
10
Department of Periodontology, Faculty of Dental Medicine, Hebrew University‐Hadassah Medical Center, Jerusalem, Israel
11
Periodontal Department, Tufts University School of Dental Medicine, Boston, MA, USA
12
Periodontology, Section 1, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
13
Department of Periodontology, University of Iowa College of Dentistry, Iowa City, IA, USA
14
Orofacial Sciences, University of California San Francisco, USA
15
Department of Periodontology, University of Bern, Switzerland
16
Department of Periodontology, University of Giessen, Germany
17
Department of Periodontology, Graduate School of Dentistry, Osaka University, Japan
18
Department of Periodontics, Texas A&M College of Dentistry, Dallas, TX, USA
19
Division of Periodontology, Department of Stomatology, Dental School, University of São Paulo, Brazil
20
Division of Periodontology, College of Dentistry, Ohio State University, Columbus, OH, USA
21
Department of Oral Health Sciences, Periodontology, KU Leuven & Dentistry, University Hospitals Leuven, Belgium
22
Research Center for the Study of Periodontal and Peri‐Implant Diseases, University of Ferrara, Italy
23
Department of Periodontology, Endodontology & Cariology, University Centre for Dental Medicine, University of Basel School of Dentistry, Switzerland
24
Department of Prosthodontics, School of Dentistry, Medical University Graz, Austria
© 2018 American Academy of Periodontology and European Federation of Periodontology
S68 | wileyonlinelibrary.com/journal/jcpe J Clin Periodontol. 2018;45(Suppl 20):S68–S77.

CHAPPLE et al. | S69
25
Orofacial Sciences, School of Dentistry, University of California San Francisco, USA
26
Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Japan
Correspondence
Dr. Iain Chapple Abstract
Email: [email protected] Periodontal health is defined by absence of clinically detectable inflammation. There
Sources of Funding: The workshop was is a biological level of immune surveillance that is consistent with clinical gingival
planned and conducted jointly by the health and homeostasis. Clinical gingival health may be found in a periodontium that
American Academy of Periodontology and
the European Federation of Periodontology is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodon-
with financial support from the American tium in either a non‐periodontitis patient (e.g. in patients with some form of gingival
Academy of Periodontology Foundation,
Colgate, Johnson & Johnson Consumer recession or following crown lengthening surgery) or in a patient with a history of
Inc., Geistlich Biomaterials, SUNSTAR, and periodontitis who is currently periodontally stable. Clinical gingival health can be re-
Procter & Gamble Professional Oral Health.
stored following treatment of gingivitis and periodontitis. However, the treated and
The proceedings of the workshop were stable periodontitis patient with current gingival health remains at increased risk of
jointly and simultaneously published in
the Journal of Periodontology and Journal of recurrent periodontitis, and accordingly, must be closely monitored.
Clinical Periodontology. Two broad categories of gingival diseases include non‐dental plaque biofilm–in-
duced gingival diseases and dental plaque‐induced gingivitis. Non‐dental plaque bio-
film‐induced gingival diseases include a variety of conditions that are not caused by
plaque and usually do not resolve following plaque removal. Such lesions may be
manifestations of a systemic condition or may be localized to the oral cavity. Dental
plaque‐induced gingivitis has a variety of clinical signs and symptoms, and both local
predisposing factors and systemic modifying factors can affect its extent, severity,
and progression. Dental plaque‐induced gingivitis may arise on an intact periodon-
tium or on a reduced periodontium in either a non‐periodontitis patient or in a cur-
rently stable “periodontitis patient” i.e. successfully treated, in whom clinical
inflammation has been eliminated (or substantially reduced). A periodontitis patient
with gingival inflammation remains a periodontitis patient (Figure 1), and comprehen-
sive risk assessment and management are imperative to ensure early prevention and/
or treatment of recurrent/progressive periodontitis.
Precision dental medicine defines a patient‐centered approach to care, and there-
fore, creates differences in the way in which a “case” of gingival health or gingivitis is
defined for clinical practice as opposed to epidemiologically in population prevalence
surveys. Thus, case definitions of gingival health and gingivitis are presented for both
purposes. While gingival health and gingivitis have many clinical features, case defi-
nitions are primarily predicated on presence or absence of bleeding on probing. Here
we classify gingival health and gingival diseases/conditions, along with a summary
table of diagnostic features for defining health and gingivitis in various clinical
situations.
KEYWORDS
allergic reaction, amalgam tattoo, aspergillosis, biofilm, blastomycosis, calcifying fibroblastic
granuloma, candidosis, chemical trauma, clinical health, coccidioidomycosis, condylomata
acuminatum, contact allergy, coxsackie virus, Crohn's disease, dental plaque‐induced
gingivitis, disease control, disease remission, disease stability, drug‐induced gingival
enlargement, drug‐induced pigmentation, dysbiosis, erythema multiforme, erythroplakia,
factitious injury, fibrous epulis, focal epithelial hyperplasia, frictional keratosis, geotricosis,
gingival pigmentation, hand foot and mouth, hereditary gingival fibromatosis, herpangina,
S70 | CHAPPLE et al.
herpes simplex, histoplasmosis, Hodgkin lymphoma, hyperglycemia, hyposalivation, intact

periodontium, leukemia, leukoplakia, lichen planus, local risk factors, lupus erythematosus,
melanoplakia, Melkersson‐Rosenthal, menstrual cycle, modifying factors, molluscum
contagiosum, mucormycosis, Mycobacterium tuberculosis, necrotizing periodontal diseases,
Neisseria gonorrhoeae, non–dental plaque‐induced gingival conditions, non‐Hodgkin
lymphoma, oral contraceptive, orofacial granulomatosis, paracoccidioidomycosis, pemphigoid,
pemphigus vulgaris, periodontal disease, peripheral giant cell granuloma, plasma cell gingivitis,
predisposing factors, pregnancy, puberty, pyogenic granuloma, reduced periodontium,
resolution of inflammation, restoration margins, sarcoidosis, scurvy, smoker's melanosis,
smoking, squamous cell carcinoma, squamous cell papilloma, stable periodontitis,
streptoccocal gingivitis, symbiosis, systemic risk factors, thermal trauma, toothbrush trauma,
Treponema pallidum, varicella zoster, vascular epulis, verruca vulgaris
“Health is a state of complete physical, mental and social well‐being

What is the spectrum of clinical periodontal health at
and not merely the absence of disease or infirmity”.1 Based upon this
a site level?
definition from the World Health Organization (WHO), it follows that
periodontal health should be defined as a state free from inflammatory What is the biology of clinical gingival health?
periodontal disease that allows an individual to function normally and Clinical gingival health is generally associated with an inflamma-
avoid consequences (mental or physical) due to current or past disease. tory infiltrate and a host response consistent with homeostasis.
Based upon this overall framework of health, periodontal health should
be predicated upon the absence of disease, as assessed clinically, asso- On a site level, how do we classify clinical gingival health?
ciated with gingivitis, periodontitis, or other periodontal conditions, and • Clinical gingival health on an intact periodontium
may include patients who have had a history of successfully treated gin- • Clinical gingival health on a reduced periodontium
givitis or periodontitis, or other periodontal conditions, who have been
and are able to maintain their dentition without signs of clinical gingival ○ Stable periodontitis patient
inflammation. Additionally, clinical periodontal health embraces physio- ○ Non‐periodontitis patient (e.g. recession, crown lengthening)
logical immune surveillance involving levels of biological and inflamma- What are the clinical features of gingival health on an intact
tory markers compatible with homeostasis.2 Periodontitis is a chronic periodontium?
inflammatory disease that currently can be successfully controlled, and Clinical gingival health on an intact periodontium is characterized
teeth can be retained for life. Periodontitis can remain stable (in remis- by the absence of bleeding on probing, erythema and edema, patient
sion) or enter periods of exacerbation. A stable periodontitis patient re- symptoms, and attachment and bone loss. Physiological bone levels
mains at higher risk for recurrent disease compared to a gingivitis patient range from 1.0 to 3.0 mm apical to the cemento‐enamel junction.
or a healthy patient. Therefore, precision dental medicine requires ongo- What are the clinical features of gingival health on a reduced
ing, individual risk assessment as part of optimal patient management. periodontium?
A definition of periodontal health and wellness is critical to es- Clinical gingival health on a reduced periodontium is character-
tablish ideal and acceptable therapeutic end points to periodontal ized by an absence of bleeding on probing, erythema, edema and
therapies, to systematically assess the biological burden of peri- patient symptoms in the presence of reduced clinical attachment
odontal inflammation, to categorize gingival and periodontal disease and bone levels. However, it should be recognized that successfully
prevalence in populations, and to evaluate individualized risk for treated and stable periodontitis patients remain at increased risk of
future disease development. Periodontal health must be assessed recurrent progression of periodontitis. In non‐periodontitis patients,
and defined at both the patient and site level to achieve these goals. there is no current evidence for increased risk of periodontitis.
Furthermore, definitions of periodontal health that are used to in- What are the clinical features of gingival health following treatment
form treatment decisions for individual patients may differ from of gingivitis on an intact periodontium?
those used in epidemiological studies. Clinical gingival health following treatment of gingivitis on an intact
periodontium is characterized by the absence of bleeding on probing,
erythema and edema, patient symptoms, and attachment and bone loss.
Is there a level of gingival inflammation that is
What are the clinical features of gingival health following successful
consistent with clinical periodontal health at a site
treatment of periodontitis?
level?
Clinical gingival health following successful treatment of peri-
There is a biological level of immune surveillance, manifesting as a odontitis is characterized by an absence of bleeding on probing, er-
predominantly neutrophilic infiltrate that is consistent with clinical ythema, edema, and patient symptoms in the presence of reduced
gingival health. 2 clinical attachment and bone levels.
C A S E D E FI N ITI O N S FO R PE R I O D O NTA L at isolated sites is ubiquitous, but may fall within the spectrum of
H E A LTH A N D G I N G I V ITI S “clinical health”.
In clinical practice, a case of gingival health on an intact peri-
Based on available methods to assess gingival inflammation, a gin- odontium would be a patient with no signs of gingivitis as defined
givitis case can be simply, objectively and accurately defined and above.
3
graded using a bleeding on probing score (BOP%), assessed as In clinical practice, the goal of periodontal treatment on a re-
the proportion of bleeding sites (dichotomous yes/no evaluation) duced periodontium is a patient with no signs of gingivitis as de-
when stimulated by a standardized (dimensions and shape) perio- fined above. A case of gingival health on a reduced periodontium in
dontal probe with a controlled (∼0.25 N) force to the apical end of a stable periodontitis patient must be distinguished from a case of
the sulcus at six sites (mesio‐buccal, buccal, disto‐buccal, mesio‐ periodontal health in a reduced periodontium in a non‐periodontitis
lingual, lingual, disto‐lingual) on all teeth present. Limitations of patient (recession, crown lengthening), because there is a difference
these clinical criteria arise from a lack of standardized periodontal in risk for periodontal disease progression.
probes (e.g. probe dimensions, taper), examiner variability (probe Following treatment of periodontitis, periodontitis patients may
pressure, angle), patient related factors (biotype, medications, not attain a status of complete gingival health based on the above
etc.) and smoking. definition. However, evidence has demonstrated that a patient may
In all references to an “intact periodontium” within this consen- achieve periodontal stability. Periodontal stability is characterized
sus, an absence of detectable attachment and/or bone loss is implicit. by successful treatment through control of local and systemic risk
factors, resulting in minimal (< 10% of sites4) BOP, no probing depths
of 4 mm or greater that bleed on probing, optimal improvement in
How do we define a case of gingival health
other clinical parameters and lack of progressive periodontal de-
on an intact and a reduced periodontium for
struction.6 The treated and stable periodontitis patient with current
epidemiological purposes?
gingival health remains at increased risk of recurrent periodontitis
For an intact periodontium and a reduced and stable periodontium, and accordingly must be closely monitored. Figure 1 summarizes the
gingival health is defined as < 10% bleeding sites4,5 with probing various scenarios that may arise following the transition from health,
depths ≤3 mm. to gingivitis and ultimately periodontitis.
How do we define a case of gingival health on How do we define gingivitis at a site level (biological &
an intact and a reduced periodontium for clinical clinical)?
practice?
Defining inflammation at a site level is quite distinct from defining a
Due to limitations in, and a lack of uptake of, standardized ISO probes case of gingivitis. A universal case definition is essential to facilitate
and techniques leading to inherent measurement variability in the population surveillance, for clinicians setting therapeutic targets,
parameters of gingival health, a patient with periodontal health may and to enable assessment of the efficacy of prevention and/or treat-
exhibit one or two sites with some evidence of clinical gingival in- ment regimes.
flammation. Moreover, localized mild and delayed bleeding to probe There are broadly two categories of gingival disease:
F I G U R E 1 The transition from periodontal health to gingivitis is reversible following treatment that resolves gingival inflammation. The
transition to periodontitis results in attachment loss which, at the present time is irreversible. More importantly, it signposts patients who
are at lifelong high risk of recurrent periodontitis. Optimal periodontal therapy can restore gingival health on a reduced periodontium, or
may result in mild marginal gingival inflammation at shallow probing pocket depths (≤ 3 mm). However, a history of periodontitis places
patients at high risk of recurrent periodontitis and such patients require careful site‐specific monitoring during periodontal maintenance
programs
• Dental plaque biofilm‐induced gingivitis niche that encourages increased plaque accumulation.7 These
• Non–dental plaque‐induced gingival diseases include:
a. Dental plaque biofilm retention factors (including certain
Dental plaque biofilm‐induced gingivitis is defined at the site level tooth anatomical factors) – facilitate plaque accumulation at
as “an inflammatory lesion resulting from interactions between the dental and apical to the gingival margin, enabling biofilm adherence
plaque biofilm and the host's immune‐inflammatory response, which re‐ and maturation and increasing the difficulty of mechanical
mains contained within the gingiva and does not extend to the periodontal plaque removal. Several clinical studies providing a moderate
attachment (cementum, periodontal ligament and alveolar bone). Such in‐ level of evidence have demonstrated that subgingival resto-
flammation remains confined to the gingiva and does not extend beyond ration margins may be detrimental to gingival health.15,16
the mucogingival junction and is reversible by reducing levels of dental b. Oral dryness is a clinical condition often associated with symp-
plaque at and apical to the gingival margin”. toms of xerostomia. Oral dryness manifesting as a lack of sali-
Depending on whether dental plaque biofilm‐induced gingival vary flow, availability, or changes in quality of saliva, leading to
inflammation occurs on an intact or reduced periodontium, or in a reduced cleansing of tooth surfaces is associated with reduced
patient diagnosed with periodontitis, gingivitis can be further clas- dental plaque biofilm removal and enhanced gingival inflamma-
sified as: tion. Common causes include medications that have anti‐para-
sympathetic action, Sjögrens syndrome when the salivary acini
• Gingivitis on an intact periodontium are replaced by fibrosis following autoimmune destruction, and
• Gingivitis on a reduced periodontium in a non‐periodontitis pa- mouth breathing in people who may have enhanced gingival
tient (e.g., recession, crown lengthening) display and/or an incompetent lip seal.17
• Gingival inflammation on a reduced periodontium in a success-
fully treated periodontitis patient (Note that recurrent periodon- 2. Systemic risk factors (modifying factors)
titis cannot be ruled out in this case)
Systemic risk or modifying factors are those characteristics pres-
Since the 1999 classification, there have been advances in knowl- ent in an individual, which negatively influence the immune‐in-
edge of the microbiome and the gingival transcriptome. Gingivitis is a flammatory response to a given dental plaque biofilm burden,
non‐specific inflammatory condition and is therefore a consequence resulting in exaggerated or “hyper” inflammation. Examples
of sustained plaque biofilm accumulation at and apical to the gingi- include:
val margin.7 Longitudinal studies have demonstrated that sites that a. Smoking – is one of the major lifestyle/behavioral risk factors
do not progress to attachment loss are characterized by less gingival for periodontitis, but which also has profound effects upon the
inflammation over time, whereas those sites that do progress have gingival tissues. Systemic circulatory uptake of components of
persistently greater levels of gingival inflammation.8‒14 Therefore, cigarette smoke as well as local uptake are reported to induce
gingivitis is a major risk factor, and a necessary pre‐requisite, for peri- microvascular vasoconstriction and fibrosis. This can mask clini-
odontitis. The management of gingivitis is thus a primary prevention cal signs of gingivitis, such as bleeding on probing, despite a sig-
strategy for periodontitis. nificant underlying pathological inflammatory cell infiltrate.18
Periodontitis patients who are currently stable but develop gingival b. Metabolic factors – hyperglycemia in people with or without
inflammation at specific sites should remain on periodontal mainte- diabetes. Excess glucose is toxic and directly induces mitochon-
nance and should be closely monitored during periodontal maintenance drial stress and an enhanced respiratory burst in inflammatory
for any reactivation of periodontitis. Such patients may not be managed cells that may activate various proinflammatory mediator cas-
in the same way as non‐periodontitis patients with gingivitis. cades. Formation of advanced glycation end‐products (AGEs)
may also result in AGE binding to its cell surface receptor
(RAGE), which activates proinflammatory signaling cascades
What are the determinants of the rate of
and downstream proinflammatory events.19
development of gingivitis, its severity and extent?
c. Nutritional factors – Severe Vitamin C deficiency, or scurvy,
The threshold of plaque accumulation necessary to induce gingival results in compromised antioxidant micronutrient defenses to
inflammation and impact upon its rate of progression at specific sites oxidative stress and also negatively impacts collagen synthe-
or at a whole mouth level varies between individuals according to sis, resulting in weakened capillary blood vessel walls and a
both local risk factors, known as predisposing factors, and systemic consequent propensity to enhanced gingival bleeding. 20
risk factors, referred to as modifying factors, respectively. d. Pharmacological agents (prescription, non‐prescription, and
recreational agents) – can act via diverse mechanisms to in-
1. Local risk factors (predisposing factors) crease susceptibility to gingivitis. This may include drugs that
Local risk factors for gingivitis are those that encourage plaque reduce salivary flow, drugs that impact endocrine function
accumulation at a specific site by either inhibiting its removal (see below), and drugs that may induce gingival enlargement
during daily oral hygiene practices, and/or creating a biological and pseudo‐pocketing.
e. Elevations in sex steroid hormones – at puberty, during preg- 4. The symptoms a patient may report include:
nancy, or following medication with first generation oral con- a. Bleeding gums (metallic/altered taste)
traceptives may modify the gingival inflammatory response. b. Pain (soreness)
Complex biological reactions within the gingival tissues result c. Halitosis
from such elevated sex steroid levels and generate more than d. Difficulty eating
expected inflammation, in response to relatively small levels e. Appearance (swollen red gums)
of plaque. However, modern oral contraceptive dosages have f. Reduced oral health–related quality of life
been reduced and there is little evidence for exaggerated gin- 5. Radiographs cannot be used to diagnose gingivitis.
gival inflammatory responses to plaque with such drugs. 21
f. Hematological conditions – particular blood malignancies such
Should we classify dental plaque biofilm‐induced
as leukemia or pre‐malignant conditions such as myelodyspla-
gingivitis?
sia are associated with signs of excess gingival inflammation in
the absence of excessive plaque biofilm accumulation. Signs There is utility in defining the severity of gingivitis as a patient commu-
include swollen, purple or occasionally pale gingiva due to nication tool, but there are no objective clinical criteria for defining se-
leukemic cell infiltration, gingival bleeding that is inconsis- verity. Thus, in this context alone, the extent of gingivitis can be used
tent with levels of dental plaque biofilm accumulation, due to to communicate “mild, moderate, and severe” gingivitis. Moreover,
thrombocytopenia and/or clotting‐factor deficiencies. 22 emerging evidence suggests that the contained gingivitis lesion may
have systemic inflammatory consequences.23,24
There is no robust evidence to clearly differentiate mild, moder-
What are the diagnostic criteria for a gingivitis case?
ate, and severe gingivitis, and definitions remain a matter of profes-
Given the “spectrum” of presentation of gingival health and gingival sional opinion. Methods of defining gingivitis may include:
inflammation in terms of severity and extent of gingival involvement,
it is important to define the features of a universally accepted case Defining percentages (e.g. mild = < 10%, moderate = 10%‐30%, se-
of gingivitis. vere = > 30% sites)
Current epidemiological data on the prevalence of gingivitis suf- Grading (e.g. grade 1 to 5 in 20% quintiles for % sites bleeding on
fer from the lack of a universally adopted case definition and vary as probing).
widely as 6% to 94%, due to the use of indices that measure gingival
inflammation at individual sites rather than considering the patient's
mouth as a whole. Therefore, mild localized clinical inflammation is
How do we define a case of dental plaque‐induced
reported to affect almost 95% of the population, a figure that would
gingivitis on an intact and a reduced periodontium for
incorrectly suggest gingivitis as being a variation of “normality” and
epidemiological purposes?
thus consistent with the spectrum of “clinical health” rather than
being a disease. By contrast, the more extensive the manifestation For epidemiological purposes, gingivitis on an intact periodontium and
of disease employed in a case definition, the lower the reported gingivitis on a reduced periodontium in a patient without a history of
prevalence. A universally agreed case definition should be based periodontitis, is defined as ≥10% bleeding sites4,5 with probing depths
upon a pragmatic appraisal of the evidence base derived from longi- ≤3 mm. Localized gingivitis is defined as 10%‐30% bleeding sites; gen-
tudinal observation and intervention studies. eralized gingivitis is defined as > 30% bleeding sites.
For epidemiological purposes alone, a periodontitis case cannot
Clinical, radiological, and biological signs and symptoms simultaneously be defined as a gingivitis case. Therefore, a patient
with a history of periodontitis, with gingival inflammation is still a
1. Gingivitis is a clinical diagnosis. While emerging technologies periodontitis case.
are starting to shed light on the microbiological, molecular,
and pathophysiological characteristics of gingivitis, definitive
How do we classify a patient with dental plaque‐
knowledge is not sufficient to supersede current clinical
induced gingivitis on an intact and a reduced
parameters.7
periodontium for clinical practice?
2. The clinical signs of inflammation are erythema, edema, pain
(soreness), heat, and loss of function. In clinical practice, a case of gingivitis on an intact periodontium, or
3. These may manifest clinically in gingivitis as: a reduced periodontium in a patient without a history of periodonti-
a. Swelling, seen as loss of knife‐edged gingival margin and tis, would be a patient with signs of gingival inflammation as defined
blunting of papillae above (Table 1).
b. Bleeding on gentle probing In clinical practice, periodontitis patients, if successfully treated
c. Redness can achieve a reduced and stable periodontium where probing pocket
d. Discomfort on gentle probing depths are ≤4 mm27 and there is an absence of clinical inflammation
TA B L E 1 Diagnostic look‐up table for gingival health or dental plaque‐induced gingivitis in clinical practice
Intact periodontium Health Gingivitis
Probing attachment loss No No

a
Probing pocket depths (assuming no pseudo pockets) ≤3 mm ≤3 mm
Bleeding on probinga <10% Yes (≥ 10%)
Radiological bone loss No No
Reduced periodontium
Non‐periodontitis patient Health Gingivitis
Probing attachment loss Yes Yes

a
Probing pocket depths (all sites & assuming no pseudo pockets) ≤3 mm ≤3 mm
Radiological bone loss Possible Possible
NB: In conditions where there is treatment but not cure, e.g. rheumatoid arthritis, periodontitis, the post‐treatment parameters that define
stability/health or gingivitis may differ from the parameters for health/gingivitis in a non‐periodontitis patient. The threshold for “clinical health”
in a treated and stable periodontitis patient is therefore set at ≤ 4 mm.
Gingivitis in a patient
with a history of
Successfully treated stable periodontitis patient Health periodontitis
Probing attachment loss Yes Yes

Probing pocket depths (all sites & assuming no pseudo pockets)a ≤4 mm (no ≤3 mm
site ≥ 4 mm
with BOP)b
Radiological bone loss Yes Yes
NB: A successfully treated periodontitis patient in whom sites of gingival bleeding appear remains at high risk of disease recurrence at those sites
and of progressive attachment loss. Therefore, gingivitis is defined as bleeding at a shallow site of ≤ 3 mm rather than ≤ 4 mm, as is the case in
gingival heath. Where the probing depth is 4 mm or higher with bleeding, this is no longer a “closed pocket.”21,27
a
Assumes a light probing pressure of 0.2 to 0.25 N.
b
There was a rational minority view expressed that the threshold for defining a clinical case of health in a successfully treated periodontitis patient
should be set at ≤ 3 mm with no BOP to acknowledge the elevated risk of recurrent disease. However, the counter and majority view was that the ≤ 3
mm threshold is rarely achieved at 100% of treated sites and could lead to over‐treatment, since any non‐bleeding site > 3 mm would not be classified
as “health” and thus open to further invasive treatment, rather than monitoring and supportive care. The threshold was therefore set at ≤ 4 mm ac-
knowledging that post‐treatment clinical phenotypes need to be considered differently to pre‐treatment phenotypes.
(bleeding on probing). Gingival inflammation may arise at specific sites, do not resolve following plaque removal. Such lesions may be
and where probing depths are ≤ 3 mm is termed gingival inflammation manifestations of a systemic condition or may be localized to
in a stable periodontitis patient. However, such patients remain at high the oral cavity. 25 Although these lesions are not caused by the
risk of recurrent periodontitis and require close monitoring as such dental plaque biofilm, the severity of the clinical manifestations
sites are at high risk of reverting to periodontitis (Table 1). often depends on plaque accumulation and subsequent gingival
inflammation. 26
The proposed classification considers those conditions listed in
How do we classify non–dental plaque‐induced
Table 2.
gingival conditions?
Although oral health and systemic health are frequently consid-
Which non–dental plaque‐induced gingival conditions
ered as separate entities, both are strongly interrelated. There are
may have associated systemic involvement and
numerous examples of how oral diseases may impact systemic
how does that impact upon patient‐centered care
health and how the oral cavity may be a window to general health.
pathways?
Consequently, it is crucial for all health‐care providers to understand
these interrelationships, inform patients of such conditions, and In recent years, the traditional treatment model in which the pa-
make appropriate referrals. tient was a passive receiver of care is changing toward patient‐
Non‐dental plaque‐induced gingival conditions encompass a centered care in precision dental medicine (PDM). In PDM, an
variety of conditions that are not caused by plaque and usually individual's specific health needs and desired health outcomes
TA B L E 2 Classification of gingival health and gingival diseases/ TA B L E 2 (Continued)

conditions
(Continues)
(Continues)
TA B L E 2 (Continued) 1. Tip diameter 0.5 mm

2. Cylindrical tine structure
3. Constant force limiter of 0.25 N
4. 15‐mm scale with precise individual or banded millimeter
markings
5. A taper of 1.75°
AC K N OW L E D G M E N T S A N D D I S C LO S U R E S
Workshop participants filed detailed disclosure of potential conflicts

a
Conditions marked with an “a” have associated systemic involvement of interest relevant to the workshop topics, and these are kept on
or are oral manifestations of systemic conditions; therefore, other
file. The authors receive, or have received, research funding, con-
health‐care providers may be involved in diagnosis and treatment.
sultant fees, and/or lecture compensation from the following com-
panies: 3D Matrix, BioGaia AB, BioHorizons, Boehringer Ingleheim,
are the driving force behind all health‐care decisions and qual- CALCIVIS, Cigna, Colgate, CP GABA, Dentaid, Dentsply Sirona, Dexcel
ity measurements. One of the elements in PDM is that care is Pharma, EMS Dental, GC Corporation, Geistlich, GlaxoSmithKline,
collaborative, coordinated, and accessible. The right care is pro- Hain Lifescience, Intra‐Lock, ISOThrive, ITI Foundation, Ivoclar‐
vided at the right time and the right place. Considering that the Vivadent, Johnson & Johnson, Kaken Pharmaceutical, Kulzer Dental,
conditions marked with an “a.” (Table 2) have associated systemic Lion Corporation, Millennium Dental Technologies, MIS Implants,
involvement or are oral manifestations of systemic conditions, Mitsubishi Chemical, National Safety Associates, Nobel Biocare,
other health‐care providers may be involved in diagnosis and Noveome Biotherapeutics, OraPharma, Osteogenics Biomedical,
treatment. Philips, Procter & Gamble, Reminova, Schülke & Mayr, Straumann,
SUNSTAR, Thommen Medical, TRISA, Unilever, and Zimmer Biomet.
FU T U R E R E S E A RC H N E E DS
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How to cite this article: Chapple ILC, Mealey BL, et al.
7–30.
19. Chapple ILC, Genco R. Diabetes and periodontal diseases: consen- Periodontal health and gingival diseases and conditions on an
sus report of the Joint EFP/AAP Workshop on Periodontitis and intact and a reduced periodontium: Consensus report of
Systemic Disease. J Clin Periodontol. 2013;40(S14):106–112. workgroup 1 of the 2017 World Workshop on the
20. Van der Velden U, Kuzmanova D, Chapple ILC. Micronutritional
approached to periodontal therapy. J Clin Periodontol.
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21. Trombelli L, Farina R. A review of factors influencing the inci- https://doi.org/10.1111/jcpe.12940
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FIGURE 1 Participants of Workgroup 1

Received: 8 February 2017 | Revised: 8 August 2017 | Accepted: 19 August 2017
DOI: 10.1111/jcpe.12937
2017 WORLD WORKSHOP
Dental plaque–induced gingival conditions
Shinya Murakami1 | Brian L. Mealey2 | Angelo Mariotti3 | Iain L.C. Chapple4
1
Osaka University, Graduate School of
Dentistry‐Department of Periodontology, Abstract
Osaka, Japan Objective: This review proposes revisions to the current classification system for
2
Department of Periodontics, The University
gingival diseases and provides a rationale for how it differs from the 1999 classifica‐
of Texas Health Science Center at San
Antonio, San Antonio, TX, USA tion system.
3
Division of Periodontology, College of Importance: Gingival inflammation in response to bacterial plaque accumulation (mi‐
Dentistry, The Ohio State University,
crobial biofilms) is considered the key risk factor for the onset of periodontitis. Thus,
Columbus, OH, USA
4
Department of Periodontology, University control of gingival inflammation is essential for the primary prevention of
of Birmingham School of Dentistry, periodontitis.
Birmingham, UK
Findings: The clinical characteristics common to dental plaque–induced inflamma‐
Correspondence tory gingival conditions include: a) clinical signs and symptoms of inflammation that
Prof. Shinya Murakami, Osaka University,
Graduate School of Dentistry‐Department are confined to the gingiva: b) reversibility of the inflammation by removing or dis‐
of Periodontology, Osaka, Japan. rupting the biofilm; c) the presence of a high bacterial plaque burden to initiate the
Email: [email protected]
inflammation; d) systemic modifying factors (e.g., hormones, systemic disorders,
The proceedings of the workshop were drugs) which can alter the severity of the plaque‐induced inflammation and; e) stable
the Journal of Periodontology and Journal of (i.e., non‐changing) attachment levels on a periodontium which may or may not have
Clinical Periodontology. experienced a loss of attachment or alveolar bone. The simplified taxonomy of gingi‐
val conditions includes: 1) introduction of the term “incipient gingivitis;” 2) a descrip‐
tion of the extent and severity of gingival inflammation; 3) a description of the extent
and severity of gingival enlargement and; 4) a reduction of categories in the dental
plaque–induced gingival disease taxonomy.
Conclusions: Dental plaque–induced gingival inflammation is modified by various
systemic and oral factors. The appropriate intervention is crucial for the prevention
of periodontitis.
KEYWORDS
diagnosis, evidence‐based dentistry, gingivitis
Plaque‐induced gingivitis may exhibit various patterns of observ‐ an incipient dysbiosis (Figure 1). Various systemic factors, including
able signs and symptoms of inflammation that are localized to the endocrinopathies, hematologic conditions, diet, and drugs, can mod‐
gingiva and initiated by the accumulation of a microbial biofilm on ify the immune‐inflammatory response. 2,3
teeth. Even when dental plaque biofilm levels are minimized, an in‐ Gingivitis associated with plaque and/or endogenous hormonal
flammatory infiltrate is present within gingival tissues as part of a fluctuations, drugs, systemic diseases, and malnutrition, exhibit several
physiologic immune surveillance.1 However, the initiation of gingivi‐ essential characteristics. The universal features of these gingival condi‐
tis occurs if dental plaque accumulates over days or weeks without tions include: clinical signs and symptoms of inflammation that are con‐
disruption or removal, due to a loss of symbiosis between the biofilm fined to the free and attached gingiva and do not extend beyond the
and the host's immune‐inflammatory response, and development of mucogingival junction; reversibility of the inflammation by disrupting/
J Clin Periodontol. 2018;45(Suppl 20):S17–S27. wileyonlinelibrary.com/journal/jcpe | S17

S18 | MURAKAMI et al.
Behavioural risk factors absent Behavioural risk factors present
Environmental risk factors absent Environmental risk factors evident
Clinical Health
DAMPs
Complement
Incipient Frank Dis-
Health
Host response Dysbiosis PMNs ++ Host response Dysbiosis PMNs +++ Tissue &
Host response Haem
PMNs (Quorum (Pathogenic Bone
biofilm = (hyper-
Sensing Biofilm) ↑ GCF Damage
Symbiosis Bacteria) T & B cells Plasma cells inflammatory)
Cytokines
Virulence Prostanoids
Acute Factors Chronic
Gingipains Failed MMPs Chronic non-
Bact’l DNA
Low High High Resolving
biomass fMLP biomass LPS biomass LPS
Stress
Chapple 2015
F I G U R E 1 Contemporary model of host–microbe interactions in the pathogenesis of periodontitis, in which the host response drives an
incipient dysbiosis (gingivitis). If the biofilm is not disrupted/removed, frank dysbiosis results and perpetuates a chronic nonresolving and
destructive inflammation. DAMPs, damage‐associated molecular patterns; fMLP, N‐ formylmethionyl‐ leucyl‐ phenylalanine; GCF, gingival
crevicular fluid; LPS, lipopolysaccharide; MMPs, matrix metalloproteinases; PMNs, polymorphonuclear neutrophils. This figure is referred
from ref. 106.
removing the biofilm; the presence of a high bacterial plaque burden In addition, papers related to “gingivitis” were retrieved using
to initiate and/or exacerbate the severity of the lesion (although this Medline and were finally selected based on the discussion of the
varies among individuals); and stable (i.e., unchanging) attachment lev‐ authors and supplemented by suggestions of the co‐chairs of the
els on a periodontium, which may or may not have experienced a loss group.
of attachment or alveolar bone. Gingival inflammation is regarded as a
necessary prerequisite for the subsequent development of periodon‐
titis and progressive attachment loss around teeth.4 Management of PL AQU E‐ I N D U C E D G I N G I V ITI S
gingivitis is therefore a key primary preventive strategy for periodontitis
and a secondary preventive strategy for recurrence of periodontitis.5,6 Plaque‐induced gingivitis is an inflammatory response of the gin‐
gival tissues resulting from bacterial plaque accumulation located
at and below the gingival margin.6 It does not directly cause tooth
M E TH O D S loss; however, managing gingivitis is a primary preventive strategy
for periodontitis.7 Epidemiologic data have shown plaque‐induced
This review updates and revises the previous classification of gingivitis to be prevalent at all ages in dentate populations,8‒14 and
plaque‐induced gingival conditions reported in the 1999 classifica‐ this disease is considered the most common form of periodontal
tion system.5 A literature search was conducted using the PubMed disease15(Table 1). The initial changes from health to plaque‐in‐
interface with “Gingival diseases” [MeSH] or “Gingivitis” [MeSH] and duced gingivitis may not be detectable clinically,16 raising important
other related MeSH terms, such as “Microbiota”[MeSH], “Gonadal debates concerning clinical thresholds for defining physiologic vs
Steroid Hormones”[MeSH], “Hyperglycemia”[MeSH], “Dental pathologic inflammation. However, as plaque‐induced gingivitis pro‐
Prosthesis”[MeSH], applied to systematic and narrative reviews as gresses to more established forms of this disease, clinical signs and
well as original research articles published after 1999. Also utilized symptoms become obvious. Plaque‐induced gingivitis begins at the
were manual search approaches to identify additional primary stud‐ gingival margin and may spread throughout the remaining gingival
ies; studies relating to non‐plaque‐induced gingival lesions were not unit. Patients may notice symptoms that include bleeding with tooth
considered. brushing, blood in saliva, gingival swelling and redness, and halitosis
in the case of established forms.17
The intensity of the clinical signs and symptoms will vary among
Observations and discussion
individuals18 as well as among sites within a dentition. The com‐
5
References employed in the 1999 classification system were re‐ mon clinical signs of plaque‐induced gingivitis include erythema,
viewed, and the appropriate ones were selected for re‐analysis. edema, bleeding, tenderness, and enlargement.7,19 The severity
MURAKAMI et al. | S19
TA B L E 2 Classification of plaque‐induced gingivitis and

modifying factors
85.5% (male) 78.8% (female)
83% including periodontitis

53% (male) 44% (female)
47% (male) 39% (female)
including periodontitis
A. Associated with bacterial dental biofilm only
B. Potential modifying factors of plaque‐induced gingivitis
1. Systemic conditions
a) Sex steroid hormones
Prevalence
1) Puberty
2) Menstrual cycle
58.8%
38.7%
3) Pregnancy
4) Oral contraceptives
b) Hyperglycemia
c) Leukemia
BOP, calculus, pocket depth,

Bleeding on gentle sweep of
Bleeding on gentle sweep of

d) Smoking
e) Malnutrition
2. Oral factors enhancing plaque accumulation
the gingival margin
the gingival margin
attachment level
a) Prominent subgingival restoration margins
b) Hyposalivation
C. Drug‐influenced gingival enlargements
Definition
PI
PI
of plaque‐induced gingivitis can be influenced by tooth and root

anatomy, restorative and endodontic considerations, and other
tooth‐related factors20 (Table 2). Radiographic analysis and/or
National survey
National survey
National survey
National survey
National survey
probing attachment levels of individuals with plaque‐induced gin‐

Method
givitis will generally not indicate loss of supporting structures.

Histopathologic changes include the elongation of rete ridges into
the gingival connective tissue, vasculitis of blood vessels adjacent
to the junctional epithelium, progressive destruction of the colla‐
Sample size
gen fiber network with changes in collagen types, cytopathologic

15,132
alterations of resident fibroblasts, and a progressive inflammatory/

11,111
5,686
6,469
6,672
7,109
immune cellular infiltrate.16 Although recent studies suggest that

bacterial phylotypes associated with gingivitis are distinct from
those associated with health or periodontitis, 21‒24 further studies
Age, years
are needed to clearly define the microbial community of gingivi‐

65‐80+
18‐64
18‐79
14‐17
tis. In this regard, gingivitis is a non‐specific dental plaque–induced

6‐11
16+
inflammatory condition, a concept that remains unchanged from

1999.
Adults in U.K. excluding
The molecular characteristics or the pattern of the gingival

Employed adults in U.S.
Retired persons in U.S.

School children in U.S.
Employed adults and
transcriptome (i.e., sum total of all mRNA expressed by genes

found in the gingiva) during plaque‐induced gingival inflamma‐
Children in U.S.
seniors in U.S.
Summary of epidemiologic studies on gingivitis
tion have been scrutinized since the last classification work‐

Population
Scotland
shop. Because mRNA transcripts are not always translated into

proteins, it is important to understand which transcripts are ex‐
pressed as proteins25 and causally related to the onset of gingi‐
PI, periodontal index; BOP, bleeding on probing
val inflammation, and which are risk factors or risk predictors of

2012
1991
1987
1972
1965
gingival inflammation. Currently, several broad biologic changes

Year
in the transcription of genes from non‐inflamed to inflamed gin‐

gival units have been documented, and ontologic groupings and
U.S. Public Health
U.S. Public Health
U.S. Public Health
include: 1) host‐bacterial interactions, including but not limited to

Service NCHS
Service NCHS
Service NIDR
microbial pattern recognition molecules; 2) host cell chemotaxis;

White et al.
3) phagocytosis and degranulation; 4) novel cellular/molecular

Author
pathway signaling, including but not limited to cytokine signaling

Bhat
and cell adhesion; 6) T lymphocyte response; 7) angiogenesis; and

TA B L E 1
8) epithelial immune response. 26,27 At this time, the role of the

gingival transcriptome is only beginning to be understood in rela‐
Ref.
12
15
11
8
tion to gingival inflammation.

However, most clinical studies have shown there are only modest in‐
Plaque‐induced gingivitis on a reduced periodontium
flammatory changes that may be observable during ovulation.33,34,36
Following active periodontal treatment and the resolution of in‐ More specifically, gingival crevicular fluid flow has been shown to
flammation from periodontitis, the periodontal tissue is clinically increase by at least 20% during ovulation in over 75% of women
non‐inflamed but with a reduced connective tissue attachment and tested,38 and other studies have also shown a modest change in
alveolar bone height. Plaque‐induced gingivitis on a reduced perio‐ women with pre‐existing periodontal inflammation. Although there
dontium is characterized by the return of bacterially induced inflam‐ may be a very small cohort of women who are extremely sensitive
mation to the gingival margin on a reduced periodontium with no to hormonal changes in the gingiva during the menstrual cycle, most
evidence of progressive attachment loss (i.e., no indication of active women with menstrual cycle–associated gingival inflammation will
disease). The common clinical and microbial findings are the same as present with clinically non‐detectable signs of the condition39‒41
plaque‐induced gingivitis on a full periodontium except for the pres‐ (Table 3).
ence of pre‐existing attachment loss and therefore a higher risk of
periodontitis, unless professional, tailored supportive care regimens
Pregnancy
are in place. 28
During pregnancy, the prevalence and severity of gingivitis has been
reported to be elevated and frequently unrelated to the amount of
M O D I F Y I N G FAC TO R S O F PL AQU E‐
plaque present.38,42‒45 Both longitudinal and cross‐sectional stud‐
I N D U C E D G I N G I V ITI S
ies have found the prevalence and severity of gingival inflamma‐
tion significantly higher in the pregnant vs the post‐partum patient,
Plaque‐induced gingivitis exacerbated by sex steroid
even though plaque scores remained the same between the two
hormones
groups.38,42 Furthermore, gingival probing depths are deeper,38,42,44
Homeostasis within the periodontium involves complex, multifactorial bleeding on probing or bleeding with toothbrushing is also in‐
endocrine relationships.29,30 Evidence has accrued to show that tis‐ creased,42,44 and gingival crevicular fluid flow is elevated38 in preg‐
sue responses within the periodontium are modulated by androgens, nant women. The features of pregnancy‐associated gingivitis are
estrogens, and progestins at one time or another in a person's life.29,30 similar to plaque‐induced gingivitis, except the propensity to de‐
For endocrinotropic conditions, plaque bacteria in conjunction with velop frank signs of gingival inflammation in the presence of a rela‐
elevated steroid hormone levels are necessary to produce a gingival tively small amount of plaque during pregnancy.
inflammatory response. The composition of the required flora has not Pregnancy may also be associated with the formation of preg‐
been fully elucidated;31 therefore, bacteriologic analysis of endocrino‐ nancy‐associated pyogenic granulomas. This topic is covered by
tropic gingival conditions is not currently useful for diagnosis.29,30 The Holmstrup et al. from this workshop.46
following conditions may modify plaque‐induced gingivitis but are not
considered diagnoses in and of themselves (Table 2).
Oral contraceptives
Oral contraceptive agents were once associated with gingival in‐
Puberty
flammation and gingival enlargements. In the early studies, the in‐
The incidence and severity of gingivitis in adolescents are influenced creased gingival inflammation or enlargement was reversed when
by a variety of factors, including dental plaque biofilm levels, dental oral contraceptive use was discontinued or the dosages reduced.
10
caries, mouth breathing, crowding of the teeth, and tooth eruption. The features of gingivitis associated with oral contraceptives in
However, the dramatic rise in steroid hormone levels during puberty premenopausal women were similar to plaque‐induced gingivitis,
has a transient effect on the inflammatory status of the gingiva. 29,30 except the propensity to develop frank signs of gingival inflamma‐
A number of studies have demonstrated an increase in gingival in‐ tion in the presence of relatively small amounts of plaque in women
flammation of circumpubertal age and in both genders, without a taking these hormones. Current oral contraceptive concentrations
concomitant increase in plaque levels.32‒35 Although puberty‐asso‐ are much lower than the original doses that were reported in these
ciated gingivitis has many of the clinical features of plaque‐induced early clinical studies, and it is known that current formulations of
gingivitis, it is the propensity to develop frank signs of gingival in‐ oral contraceptive do not induce the clinical changes in gingiva that
flammation in the presence of relatively small amounts of plaque were reported with high‐dose contraceptives. 29,30,47
during the circumpubertal period that are key to distinguishing this
condition.
PL AQU E‐ I N D U C E D G I N G I V ITI S
E X AC E R BATE D BY S YS TE M I C CO N D ITI O N S
Menstrual cycle
During the menstrual cycle, significant and observable inflammatory Hyperglycemia, hematologic malignancies, and nutrient deficien‐
changes in the gingiva have been documented in case reports.36,37 cies are a remarkably diverse collection of systemic states that can
MURAKAMI et al.
TA B L E 3 Summary of studies on menstrual cycle‐associated gingival changes
Ref. Author Year Population Age, years Sample size Evaluation Outcome
39 Baser et al. 2009 Female dental students 19‐23 27 PI, GI no change between MD, OD,
in Turkey PgD
BOP more in PgD than MD and OD
GCF amount more in PgD than OD
IL‐1β, TNF‐α in GCF more IL‐1β in PgD than MD
and OD
40 Becerik et al. 2010 Premenopausal women 21‐40 50 (25 gingivitis, 25 healthy BOP more in PM than OV and ME
in Turkey subjects) of gingivitis subjects
PI more in gingivitis than healthy
subjects; same in OV, PM,
ME
GCF amount more in gingivitis than healthy
subjects; same in OV, PM,
ME
IL‐6, PGE2, PAI‐2, t‐PA in GCF more IL‐6 in gingivitis than
healthy subjects; same in OV,
PM, ME
41 Shourie et al. 2012 Premenopausal women 18‐40 100 (25 gingivitis, 25 gingivitis PI identical in OV, PM, ME
in India treated, 50 no existing gingivitis)
GI OV > PM > ME in gingivitis
subjects but no difference in
treated and no existing
gingivitis subjects
GCF amount OV > PM > ME in gingivitis
subjects but no difference in
treated and no existing
gingivitis subjects
PI: periodontal index; GCF: gingival crevicular fluid; ME: menstruation; PM: premenstruation; OV: ovulation; MD: the first menstruation day; OD: estimated ovulation day; PgD: estimated progesterone
secretion day; IL, interleukin; TNF‐α, tumor necrosis factor‐alpha; PGE2, prostaglandin E2; PAI‐2, plasminogen activator inhibitor‐2; t‐PA, tissue plasminogen activator.
|
S21
affect the gingival tissues. For specific systemic conditions, such as information available regarding the effects of almost all nutritional
hyperglycemia, acute leukemias, and/or vitamin C deficiency, plaque deficiencies on human periodontal tissues. The one nutritional de‐
bacteria are necessary to produce a gingival response. ficiency that has well‐documented effects on the periodontium
involves depletion of plasma ascorbic acid (i.e., vitamin C). Even
though scurvy is unusual in areas with an adequate food supply,
Hyperglycemia
certain populations on restricted diets (e.g., infants from low socio‐
Gingivitis is a consistent feature found in children with poorly con‐ economic families, the institutionalized elderly, and alcoholics) are
trolled type 1 diabetes mellitus, and the level of glycemic control at risk of developing this condition.60 Although there is no dispute
may be more important in determining the severity of gingival in‐ about the necessity of dietary ascorbic acid for periodontal health,61
flammation than the quality of plaque control.48‒50 In adults with in the absence of frank scurvy, the effect of declining ascorbic acid
diabetes mellitus it is much more difficult to detect the effects of this levels on the gingiva can be difficult to detect clinically,62 and when
endocrine disease on gingival diseases, and only limited evidence is it is detected, it usually has characteristics that are similar to plaque‐
available51 since most studies have evaluated gingival inflammation induced gingivitis.
52
in association with attachment loss.
PL AQU E‐ I N D U C E D G I N G I V ITI S
Leukemia
E X AC E R BATE D BY O R A L FAC TO R S
Oral manifestations have been described primarily in acute leukemia
and consist of cervical lymphadenopathy, petechiae, and mucosal The onset and progress of gingival inflammation can be modified/
ulcers as well as gingival inflammation and enlargement.53 Signs of exacerbated by various oral (local) factors as documented below.
inflammation in the gingiva include swollen, glazed, and spongy tis‐
sues which are red to deep purple in appearance.54 Gingival bleed‐
Prominent subgingival restoration margins
ing is a common sign in patients with leukemia and is the initial oral
sign and/or symptom in 17.7% and 4.4% of patients with acute and The subgingival convexity and margin of a restoration is very impor‐
chronic leukemias, respectively.53 The bleeding is due to thrombo‐ tant in site‐specific plaque control and is closely related to gingival
cytopenia and clotting factor deficiencies and can present in preleu‐ health. Although higher level clinical evidence in the field is not avail‐
kemic states such as myelodysplasia as an initial sign.55 Gingival able, the concept that restoration margins placed apical to the gin‐
enlargement has also been reported, initially beginning at the inter‐ gival margin are detrimental to gingival health has been confirmed
dental papilla followed by the marginal and attached gingiva. 53,54 by a 26‐year longitudinal study.63 Prominent subgingival restoration
The enlargement is caused by infiltration of gingivae by leukemic margins promote gingivitis by increasing the local accumulation of
cells.55 Although local irritants can predispose to exacerbate the gin‐ bacterial plaque. Thus, subgingival restoration margins need to be
gival response in leukemia, they are not prerequisites for lesions to carefully designed in order to minimize plaque retention.
form in the oral cavity.54
Hyposalivation
Smoking
Xerostomia is a symptom caused by a perceived lack of saliva in the
Epidemiologic studies have revealed that smoking is one of the major oral cavity, rather than a diagnosis per se;64,65 hence, the term “hy‐
lifestyle‐related environmental risk factors for periodontal disease.56 posalivation” is employed here as a diagnostic term. It is known that
Both the local and systemic effects of cigarette smoke should be in‐ some health conditions/diseases such as Sjögren's syndrome, anxiety,
trinsically considered. Inhaled cigarette smoke is absorbed from the and poorly controlled diabetes may cause xerostomia due to hypo‐
capillary vessels via the pulmonary alveolar epithelium and enters salivation. Importantly, it is frequently observed as a side effect of
the systemic circulation, whereas direct exposure of inhaled ciga‐ medications such as antihistamines, decongestants, antidepressants,
rette smoke to periodontal tissues causes vasoconstriction of the antihypertensive medications. Hyposalivation may cause progressive
periodontal microvasculature and gingival fibrosis, which is often dental caries, taste disorders, halitosis, and inflammation of the oral
observed in smokers.57 Although plaque accumulation and disease mucosa, tongue, and gingiva.66,67 Dryness in the mouth may make
progression are exacerbated in smokers, smokers have fewer clinical plaque control difficult, and gingival inflammation may be worsened.
signs and symptoms of gingival inflammation, and therefore smoking
can mask an underlying gingivitis.58,59
D RU G ‐ I N FLU E N C E D G I N G I VA L
E N L A RG E M E NT S
Malnutrition
The precise role of nutrition in the initiation or progression of peri‐ There are an assortment of medications that have been reported to
odontal diseases remains to be elucidated, leading to a paucity of affect the size of the gingival tissues.68 In the literature, the drugs
primarily associated with gingival tissue enlargement have included gingivitis” where, by definition, only a few sites are affected by mild
the antiepileptic drugs phenytoin and sodium valproate, certain cal‐ inflammation, expressed as mild redness and/or a delayed and bro‐
cium channel–blocking drugs (e.g., nifedipine, verapamil, diltiazem, ken line of bleeding rather than edema or an immediate unbroken
amlodipine, felodipine), immunoregulating drugs (e.g., ciclosporine), line of bleeding on probing. Incipient gingivitis may be regarded as
and high‐dose oral contraceptives.69‒71 For drug‐influenced gingival a condition that is part of a spectrum of “clinical health,” but may
conditions, plaque bacteria in conjunction with the drug are neces‐ rapidly become localized gingivitis if untreated. The severity, or
sary to produce a gingival response. Nonetheless, not all individuals intensity of inflammation at a site, tooth, or the entire dentition,
who take these medications will develop enlargements of the gin‐ would be reflected by the gingival index described by Loe (1967).77
gival tissues, suggesting a susceptibility requiring specific charac‐ More specifically, mild gingival inflammation would be an area with
72
teristics. Furthermore, some sites/patients with drug‐influenced a minor change in color and little change in the texture of the tis‐
gingival enlargement present little, if any, clinically evident gingivitis sue. Moderate gingival inflammation would be an area with glazing,
at affected sites. redness, edema, enlargement, and bleeding upon probing; severe
The common clinical characteristics of drug‐influenced gingival gingival inflammation would be an area of overt redness and edema
enlargements include variations in interpatient or intrapatient pat‐ with a tendency toward bleeding when touched rather than probed.
terns of enlargement (i.e., genetic predisposition),69,70 a tendency to A system to stage drug‐influenced gingival enlargements requires
occur more often in the anterior gingiva,69,70 a higher prevalence in defining the extent and severity of the enlargement. Although there
younger age groups,73‒75 onset within 3 months of use69,74,75 that is are numerous approaches to evaluate the size of the gingiva,78‒90
usually first observed at the papilla,69 and, although it can be found selection of a method that is easy to use, non‐invasive, and appro‐
in a periodontium with or without bone loss, it is not associated with priate for chairside clinical assessment was a major consideration.
attachment loss or tooth mortality.69,70,76 Finally, all of these drugs The extent of gingival enlargements were defined as either localized
produce clinical lesions and histologic characteristics that are indis‐ or generalized.91 Localized gingival enlargement was limited to the
tinguishable from one another.69,70 gingiva in relation to a single tooth or group of teeth, while gener‐
alized enlargement involves the gingiva throughout the mouth. To
be considered a gingival enlargement resulting from medications,
R E V I S I O N S TO TH E 1999 D E NTA L the size of the gingival unit must be greater than would normally
PL AQU E–I N D U C E D G I N G I VA L D I S E A S E S be expected from purely an inflammatory reaction in the gingival
C L A S S I FI C ATI O N S YS TE M tissues. Mild gingival enlargement involves enlargement of the gin‐
gival papilla; moderate gingival enlargement involves enlargement of
Plaque‐induced gingivitis can arise in any individual due to an in‐ the gingival papilla and marginal gingiva, and severe gingival enlarge‐
crease in biofilm accumulation, and gingivitis may be exacerbated ment involves enlargement of the gingival papilla, gingival margin,
by systemic states. From the previous 1999 taxonomy of plaque‐ and attached gingiva.90
induced gingival conditions, it is believed the classification can be The catalog of dental plaque–induced gingival diseases has been
simplified to represent society's current perception of disease condensed to accurately reflect the most common conditions afflict‐
and health, which has been influenced by our expanding scientific ing the gingiva, thereby simplifying the system for clinicians (Table 1).
knowledge base as well as our cultural, social, and individual value As a result of shifting circumstances represented by the patient, the
judgments. health care provider, medications, society at large, and the disease
Similar to the 1999 classification system, plaque‐induced gingi‐ itself, the classification of gingival diseases focused on those condi‐
val inflammatory conditions require the presence of dental plaque tions that were clinically identifiable in the population. Therefore,
coupled with clinical signs and symptoms of gingival inflammation in such terms as “menstrual cycle–associated gingivitis,” “oral contra‐
an otherwise stable periodontium. The revision of the 1999 classifi‐ ceptive–associated gingivitis,” and “ascorbic acid–associated gin‐
cation system for dental plaque‐induced gingival diseases involved givitis” were removed from the classification system. Specifically,
four components: 1) description of the extent and severity of the menstrual cycle–associated gingivitis was discarded because overt,
gingival inflammation, 2) description of the extent and severity of clinical signs of the disease rarely affect women. Although the clin‐
gingival enlargements, 3) a reduction in gingival disease taxonomy, ical signs of gingival inflammation that do occur may be statistically
and 4) discussion of whether mild localized gingivitis should be con‐ significant, the signs are not clinically significant and therefore not
sidered a disease or variant of health. clinically evident to the dentist. In regard to oral contraceptives, as a
To begin, the extent, or the number of gingival sites exhibit‐ result of the change to low‐dose formulations, the signs and symp‐
ing inflammation, can be described as either localized or general‐ toms of gingival inflammation are no longer observable.47 Finally,
ized. Similar to the manner in which extent is described for chronic when scurvy is considered, the existence of scurvy‐influenced gingi‐
periodontitis, a gingival condition would be described as localized val conditions is rare and more likely to result in bleeding due to de‐
when < 30% of the teeth are affected, and generalized would reflect fects in collagen cross‐linkage in the gingival tissues. The occurrence
when ≥30% of the teeth are affected by gingival inflammation. In of scurvy is unusual but may exist when there is general, severe mal‐
addition, it is proposed to consider introducing the term “incipient nutrition as found in some impoverished, underdeveloped countries.
In industrialized societies, scurvy is not a common nutritional prob‐ depend upon a symbiotic or a dysbiotic biofilm and the proportion‐
lem. Further, even when considering vitamin C deficiency (i.e., those ality of the host's immune‐inflammatory response and its ability to
with reduced but not depleted vitamin C plasma concentrations) in resolve inflammation.106
populations, the presentation of gingival inflammation is slight and It is plausible that, since gingival inflammation is a ubiquitous
indistinguishable from a plaque‐induced gingivitis. and endemic finding in children and adults worldwide and destruc‐
tion of the periodontal attachment apparatus is associated with
only a select number of inflamed gingival sites and since this is gen‐
S I G N I FI C A N C E O F D E NTA L PL AQ U E– erally not a painful nor functionally destructive state resulting in
I N D U C E D G I N G I VA L CO N D ITI O N S loss of function, gingival inflammation may not be a disease but a
variant of health. Given that inflammation is a natural and import‐
Although different types of inflammation may be features of a spe‐ ant defensive process in the body, the real problem is that when
cific diagnosis, possibly inflammation per se is not a diagnosis in gingival inflammation is discussed, it is not clear what is actually
itself. More specifically, the clinical presence or absence of an in‐ meant. The ability to determine gingival inflammation clinically re‐
flammatory response should not necessarily be considered a sign of lies upon crude tools for assessment (visual acuity and a rigid metal
disease or health. In numerous body organs, inflammation is a pro‐ probe), whereas a molecular approach, identifying genetic and epi‐
tective mechanism necessary for survival of the individual. It should genetic conditions, would clarify what type of inflammatory state
be noted that exacerbations of the inflammatory response in the gin‐ is present and identify who is at risk for future destruction of the
giva, either due to pathogenic biofilms or modified by fluctuations in periodontium. As knowledge of gingival inflammation evolves, the
sex steroid hormone secretions, may represent protective responses impact of superficial gingival inflammation on the periodontium
of an individual to both local and systemic environments by destroy‐ will become more transparent.
ing, diluting, and “walling off” the invading organisms.30 At the other The debate about the fundamental nature of disease continues
end of the spectrum, the absence of clinical signs of inflammation because of the dynamic and interactive foundation related to social
may not exclude the presence of an ongoing inflammatory process and cultural norms combined with the explosion of new scientific
evident at a histologic level. For example, during cigarette smoking, information. As a result of the shifting circumstances represented
the gingival inflammatory response to plaque accumulation on teeth by the patient, the health care provider, the basic clinical and/or
92,93
will be muted, despite distinct gingival host‐response patterns. public health scientist, society at large, and the disease itself, it is
The concept of untreated gingival inflammation progressing to essential that periodontists continue to refine the classification of
destruction of the periodontium has focused attention on plaque‐in‐ periodontal diseases and conditions through evidence from the ex‐
duced gingivitis and associated gingival conditions being part of the panding knowledge base. As a consequence of seeking to enhance
spectrum of periodontal diseases. Although this concept has been periodontal health, dentistry must continually examine the basic na‐
propagated by clinical studies showing an association between gin‐ ture of periodontal disease by seeking new knowledge; evaluating
gival inflammation and bone loss,94 longitudinal studies examining what we believe is important in our society, in our dental specialty,
the natural history of periodontal disease failed to show complete and in ourselves; acknowledging our limitations; and contemplating
93
conversion of long‐standing gingival inflammation to periodontitis. the significance of data, definitions, and classifications.
Gingival inflammation is associated with progression to periodonti‐
tis,95‒100 however, the presence of gingival inflammation does not
mean that all affected sites are destined to progress to destructive CO N C LU S I O N S
98,99
forms of periodontal disease. This information suggests that,
consistent with all complex diseases, gingival inflammation may be a It is evident that dental plaque (a microbial biofilm) causes gingi‐
sufficient cause for destruction of the periodontium but insufficient val inflammation, and the extent and severity of the inflammation
on its own to cause the disease in all people.101 More specifically, are influenced by various systemic conditions and oral factors at
how can it be determined which inflamed sites within particular indi‐ this stage. Moreover, plaque accumulates more rapidly at inflamed
viduals are susceptible to conversion to periodontitis? Presently, no gingival sites than non‐inflamed sites, creating a complex dynamic
one knows the answer to this question, but there has been an aware‐ between the dental plaque biofilm and the host's immune‐inflam‐
ness that differences in the inflammatory responsiveness of dental matory response.107 On the other hand, it should be noted that not
plaque cannot be fully accounted for by the quantity or quality of all inflammatory sites are destined to progress to periodontitis. To
the biofilm.59 In other words, the predilection for attachment loss at date, however, no scientific evidence allows us to diagnose which
inflamed gingival sites may be dependent on the susceptibility and gingivitis sites are susceptible to progression to periodontitis. Thus,
responsiveness of the individual to the inflammatory insult.102‒105 to prevent attachment loss and destruction of periodontal tissue,
Moreover, specific types of inflammatory responses in the gingiva dealing with gingivitis by appropriate local therapeutic intervention
are necessary to initiate destruction of the connective tissue attach‐ is still essential. In the future, gingival conditions may be diagnosed
ment apical to the cemento‐enamel junction. The inter‐relationships by objective analytic approaches such as transcriptome characteri‐
between health and gingivitis and periodontitis are complex and zation and/or categorization of epigenetic changes.
AC K N OW L E D G M E N T S A N D D I S C LO S U R E S 24. Shaw L, Harjunmaa U, Doyle R, et al. Distinguishing the sig‐

nals of gingivitis and periodontitis in supragingival plaque: A
The authors report no conflicts of interest related to this review cross‐sectional cohort study in Malawi. Appl Environ Microbiol.
paper. 2016;82:6057–6067.
25. Bostanci N, Ramberg P, Wahlander Å et al. Label‐free quantitative
proteomics reveals differentially regulated proteins in experimen‐
tal gingivitis. J Proteome Res. 2013;12:657–678.
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99. Schätzle M, Löe H, Lang NP, Bürgin W, Anerud A, Boysen H. 107. Hillam DG, Hull PS. The influence of experimental gingivitis on
The clinical course of chronic periodontitis. J Clin Periodontol. plaque formation. J Clin Periodontol. 1977;4:56–61.
2004;31:1122–1127.
100. Lang NP, Schätzle MA, Löe H. Gingivitis as a risk factor in peri‐
odontal disease. J Clin Periodontol. 2009;36(Suppl.10):3–8.
How to cite this article: Murakami S, Mealey BL, Mariotti A,
101. Chapple IL, Bouchard P, Cagetti MG, et al. Interaction of lifestyle,
behaviour or systemic diseases with dental caries and periodon‐
Chapple ILC. Dental plaque–induced gingival conditions.
tal diseases: Consensus report of group 2 of the joint EFP/ORCA J Clin Periodontol. 2018;45(Suppl 20):S17–S27. https://doi.
workshop on the boundaries between caries and periodontal dis‐ org/10.1111/jcpe.12937
eases. J Clin Periodontol. 2017;44(Suppl. 18):S39–S51.
Received: 9 March 2018 | Revised: 19 March 2018 | Accepted: 19 March 2018
DOI: 10.1111/jcpe.12935
2017 WORLD WORKSHOP
A new classification scheme for periodontal and peri‐implant

diseases and conditions – Introduction and key changes from
the 1999 classification
Jack G. Caton1 | Gary Armitage2 | Tord Berglundh3 | Iain L.C. Chapple4 |

Søren Jepsen5 | Kenneth S. Kornman6 | Brian L. Mealey7 | Panos N. Papapanou8 |
Mariano Sanz9 | Maurizio S. Tonetti10
1
Periodontics, Eastman Institute for Oral Health, University of Rochester, Rochester, NY, USA
2
School of Dentistry, University of California San Francisco, San Francisco, CA, USA
3
Department of Periodontology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
4
Periodontal Research Group, Institute of Clinical Sciences, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK
5
Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany
6
University of Michigan, School of Dentistry, Ann Arbor, MI, USA
7
University of Texas Health Science Center, San Antonio, TX, USA
8
Columbia University, College of Dental Medicine, New York, NY, USA
9
Facultad de Odontologia, Universidad Complutense Madrid, Madrid, Spain
10
Periodontology, Faculty of Dentistry, University of Hong Kong, Hong Kong, SAR China
Correspondence
Jack Caton, Professor and Chair, Department Abstract
of Periodontology, Eastman Institute for A classification scheme for periodontal and peri‐implant diseases and conditions is
Oral Health, University of Rochester, 625
Elmwood Avenue, Rochester, NY 14620 necessary for clinicians to properly diagnose and treat patients as well as for scien‐
Email: [email protected] tists to investigate etiology, pathogenesis, natural history, and treatment of the dis‐
Sources of Funding eases and conditions. This paper summarizes the proceedings of the World Workshop
The workshop was planned and conducted on the Classification of Periodontal and Peri‐implant Diseases and Conditions. The
jointly by the American Academy of
Periodontology and the European workshop was co‐sponsored by the American Academy of Periodontology (AAP) and
Federation of Periodontology with financial the European Federation of Periodontology (EFP) and included expert participants
support from the American Academy
of Periodontology Foundation, Colgate, from all over the world. Planning for the conference, which was held in Chicago on
Johnson & Johnson Consumer Inc., Geistlich November 9 to 11, 2017, began in early 2015.
Biomaterials, SUNSTAR, and Procter &
Gamble Professional Oral Health. An organizing committee from the AAP and EFP commissioned 19 review papers
and four consensus reports covering relevant areas in periodontology and implant
The proceedings of the workshop were
jointly and simultaneously published in dentistry. The authors were charged with updating the 1999 classification of perio‐
the Journal of Periodontology and Journal of dontal diseases and conditions1 and developing a similar scheme for peri‐implant dis‐
Clinical Periodontology.
eases and conditions. Reviewers and workgroups were also asked to establish
pertinent case definitions and to provide diagnostic criteria to aid clinicians in the use
J Clin Periodontol. 2018;45:45(Suppl 20);S1–S8. wileyonlinelibrary.com/journal/jcpe | S1

S2 | CATON et al.
of the new classification. All findings and recommendations of the workshop were
agreed to by consensus.
This introductory paper presents an overview for the new classification of perio‐
dontal and peri‐implant diseases and conditions, along with a condensed scheme for
each of four workgroup sections, but readers are directed to the pertinent consensus
reports and review papers for a thorough discussion of the rationale, criteria, and in‐
terpretation of the proposed classification. Changes to the 1999 classification are
highlighted and discussed. Although the intent of the workshop was to base classifi‐
cation on the strongest available scientific evidence, lower level evidence and expert
opinion were inevitably used whenever sufficient research data were unavailable.
The scope of this workshop was to align and update the classification scheme to
the current understanding of periodontal and peri‐implant diseases and conditions.
This introductory overview presents the schematic tables for the new classification
of periodontal and peri‐implant diseases and conditions and briefly highlights changes
made to the 1999 classification.1 It cannot present the wealth of information included
in the reviews, case definition papers, and consensus reports that has guided the
development of the new classification, and reference to the consensus and case defi‐
nition papers is necessary to provide a thorough understanding of its use for either
case management or scientific investigation. Therefore, it is strongly recommended
that the reader use this overview as an introduction to these subjects. Accessing this
publication online will allow the reader to use the links in this overview and the tables
to view the source papers (Table 1).
KEYWORDS
classification, gingivitis, peri‐implant mucositis, peri‐implantitis, periodontal diseases,
periodontitis
TA B L E 1 .
CATON et al. | S3
PE R I O D O NTA L H E A LTH , G I N G I V ITI S , A N D broad spectrum of non‐plaque induced gingival diseases and condi‐
G I N G I VA L CO N D ITI O N S 2‒ 6 tions based on primary etiology (Table 2).4
The workshop addressed unresolved issues with the previous clas‐

sification by identifying the difference between presence of gingival A N E W C L A S S I FI C ATI O N O F
inflammation at one or more sites and the definition of a gingivitis PE R I O D O NTITI S
case. It agreed that bleeding on probing should be the primary pa‐
rameter to set thresholds for gingivitis. 2,5 The workshop also char‐ The 1989 workshop recognized that periodontitis had several distinct
acterized periodontal health and gingival inflammation in a reduced clinical presentations, different ages of onset and rates of progres‐
periodontium after completion of successful treatment of a patient sion.7,8 Based on these variables the workshop categorized peri‐
with periodontitis. Specific definitions were agreed to with regard odontitis as prepubertal, juvenile (localized and generalized), adult,
to cases of gingival health or inflammation after completion of peri‐ and rapidly progressive. The 1993 European Workshop determined
odontitis treatment based on bleeding on probing and depth of the that the classification should be simplified and proposed grouping
residual sulcus/pocket. This distinction was made to emphasize the of periodontitis into two major headings: adult and early onset peri‐
need for a more comprehensive maintenance and surveillance of odontitis.9 The 1996 workshop participants determined that there
the successfully treated patient with periodontitis. It was accepted was insufficient new evidence to change the classification.10 Major
that a patient with gingivitis can revert to a state of health, but a changes were made in the 1999 classification of periodontitis,11‒13
periodontitis patient remains a periodontitis patient for life, even fol‐ which has been in use for the last 19 years. Periodontitis was reclas‐
lowing successful therapy, and requires life‐long supportive care to sified as chronic, aggressive (localized and generalized), necrotizing
prevent recurrence of disease.6 The workshop also reorganized the and as a manifestation of systemic disease.
TA B L E 2
S4 | CATON et al.
Since the 1999 workshop, substantial new information has emerged based on the primary systemic disease and be grouped as “Systemic
from population studies, basic science investigations, and the evidence Diseases or Conditions Affecting the Periodontal Supporting Tissues”.
from prospective studies evaluating environmental and systemic risk There are, however, common systemic diseases, such as uncontrolled
factors. The analysis of this evidence has prompted the 2017 workshop diabetes mellitus, with variable effects that modify the course of
to develop a new classification framework for periodontitis.14 periodontitis. These appear to be part of the multifactorial nature of
In the last 30 years, the classification of periodontitis has been re‐ complex diseases such as periodontitis and are included in the new
peatedly modified in an attempt to align it with emerging scientific ev‐ clinical classification of periodontitis as a descriptor in the staging and
idence. The workshop agreed that, consistent with current knowledge grading process.20 Although common modifiers of periodontitis may
on pathophysiology, three forms of periodontitis can be identified: substantially alter disease occurrence, severity, and response to treat‐
15
necrotizing periodontitis, periodontitis as a manifestation of systemic ment, current evidence does not support a unique pathophysiology in
disease,16 and the forms of the disease previously recognized as patients with diabetes and periodontitis.22
“chronic” or “aggressive”, now grouped under a single category, “peri‐
odontitis”.14,17‒20 In revising the classification, the workshop agreed
on a classification framework for periodontitis further characterized C H A N G E S I N TH E C L A S S I FI C ATI O N
based on a multidimensional staging and grading system that could be O F PE R I O D O NTA L D E V E LO PM E NTA L
adapted over time as new evidence emerges.20 A N D ACQ U I R E D D E FO R M ITI E S A N D
Staging is largely dependent upon the severity of disease at pre‐ CO N D ITI O N S 21 , 2 3 ‒2 5
sentation as well as on the complexity of disease management, while
grading provides supplemental information about biological features
Mucogingival conditions
of the disease, including a history based analysis of the rate of disease
progression, assessment of the risk for further progression, anticipated The new case definitions related to treatment of gingival recession
poor outcomes of treatment, and assessment of the risk that the dis‐ are based on interproximal loss of clinical attachment and also in‐
ease or its treatment may negatively affect the general health of the corporate the assessment of the exposed root and cemento‐enamel
patient.14,20 Staging involves four categories (stages 1 through 4) and is junction. 23 The consensus report presents a new classification of
determined after considering several variables including clinical attach‐ gingival recession that combines clinical parameters including the
ment loss, amount and percentage of bone loss, probing depth, pres‐ gingival phenotype as well as characteristics of the exposed root sur‐
ence and extent of angular bony defects and furcation involvement, face. 21 In the consensus report the term periodontal biotype was re‐
tooth mobility, and tooth loss due to periodontitis. Grading includes placed by periodontal phenotype (Table 4). 21
three levels (grade A – low risk, grade B – moderate risk, grade C – high
risk for progression) and encompasses, in addition to aspects related to
Occlusal trauma and traumatic occlusal forces
periodontitis progression, general health status, and other exposures
such as smoking or level of metabolic control in diabetes. Thus, grad‐ Traumatic occlusal force, replacing the term excessive occlusal force, is
ing allows the clinician to incorporate individual patient factors into the force that exceeds the adaptive capacity of the periodontium and/
the diagnosis, which are crucial to comprehensive case management or the teeth. Traumatic occlusal forces can result in occlusal trauma
(Table 3). For a complete description of the new classification scheme (the lesion) and excessive wear or fracture of the teeth.21 There is lack
for periodontitis, the reader is directed to the consensus report on of evidence from human studies implicating occlusal trauma in the
periodontitis14 and the case definition paper on periodontitis.20 progression of attachment loss in periodontitis (Table 4).24
Prosthesis‐ and tooth‐related factors

S YS TE M I C D I S E A S E S A S S O C I ATE D W ITH
LOS S O F PE R I O D O NTA L S U PP O RTI N G The section on prostheses‐related factors was expanded in the new
TI S S U E S 16 , 21 classification. The term biologic width was replaced by supracrestal
attached tissues.21 Clinical procedures involved in the fabrication of
The new classification of periodontal diseases and conditions also indirect restorations was added because of new data indicating that
includes systemic diseases and conditions that affect the periodon‐ these procedures may cause recession and loss of clinical attachment
tal supporting tissues. 16
It is recognized that there are rare systemic (Table 4).25
disorders, such as Papillon Lefèvre Syndrome, that generally result
in the early presentation of severe periodontitis. Such conditions are
grouped as “Periodontitis as a Manifestation of Systemic Disease”, A N E W C L A S S I FI C ATI O N FO R PE R I ‐
and classification should be based on the primary systemic disease. 16 I M PL A NT D I S E A S E S A N D CO N D ITI O N S 2 6
Other systemic conditions, such as neoplastic diseases, may affect the
periodontal apparatus independent of dental plaque biofilm‐induced A new classification for peri‐implant health, 27 peri‐implant mu‐
periodontitis, 21
and such clinical findings should also be classified cositis28 and peri‐implantitis29 was developed by the workshop
CATON et al. | S5
TA B L E 3
(Table 5). An effort was made to review all aspects of peri‐implant can exist around implants with normal or reduced bone support. It
health, diseases, and relevant aspects of implant site conditions and is not possible to define a range of probing depths compatible with
deformities to achieve a consensus for this classification that could peri‐implant health. 26,30
be accepted worldwide. Case definitions were developed for use by
clinicians for individual case management and also for population
Peri‐implant mucositis
studies. 26,30
Peri‐implant mucositis is characterized by bleeding on probing and
visual signs of inflammation. 28 While there is strong evidence that
Peri‐implant health
peri‐implant mucositis is caused by plaque, there is very limited evi‐
27
Peri‐implant health was defined both clinically and histologically. dence for non‐plaque induced peri‐implant mucositis. Peri‐implant
Clinically, peri‐implant health is characterized by an absence of visual mucositis can be reversed with measures aimed at eliminating the
signs of inflammation and bleeding on probing. Peri‐implant health plaque.
S6 | CATON et al.
TA B L E 4
Peri‐implantitis Hard and soft tissue implant site deficiencies

Peri‐implantitis was defined as a plaque‐associated pathologic condi‐ Normal healing following tooth loss leads to diminished dimensions of
tion occurring in the tissue around dental implants, characterized by the alveolar process/ridge that result in both hard and soft tissue de‐
inflammation in the peri‐implant mucosa and subsequent progressive ficiencies. Larger ridge deficiencies can occur at sites associated with
loss of supporting bone.29 Peri‐implant mucositis is assumed to pre‐ severe loss of periodontal support, extraction trauma, endodontic in‐
cede peri‐implantitis. Peri‐implantitis is associated with poor plaque fections, root fractures, thin buccal bone plates, poor tooth position,
control and with patients with a history of severe periodontitis. The injury and pneumatization of the maxillary sinuses. Other factors af‐
onset of peri‐implantitis may occur early following implant placement fecting the ridge can be associated with medications and systemic dis‐
as indicated by radiographic data. Peri‐implantitis, in the absence of eases reducing the amount of naturally formed bone, tooth agenesis,
treatment, seems to progress in a non‐linear and accelerating pattern.29 and pressure from prostheses.31
CATON et al. | S7
TA B L E 5 7. Caton J. Periodontal diagnosis and diagnostic aids. In: World

Workshop in Clinical Periodontics. Chicago: American Academy of
Periodontology; 1989:I1–I22.
8. Consensus report on diagnosis and diagnostic aids. In: World
Workshop in Clinical Periodontics. Chicago: American Academy of
Periodontology; 1989:I23–I31.
9. Proceedings of the 1st European Workshop on Periodontics, 1993.
London: Quintessence; 1994.
10. Papapanou PN. Periodontal diseases: epidemiology. Ann Periodontol.
1996;1:1–36.
11. Lindhe J, Ranney R, Lamster I, et al. Consensus report: chronic peri‐
odontitis. Ann Periodontol. 1999;4:38.
12. Lang N, Bartold PM, Cullinan M, et al. Consensus report: aggressive
periodontitis. Ann Periodontol. 1999;4:53.
13. Lang N, Soskolne WA, Greenstein G, et al. Consensus report: nec‐
rotizing periodontal diseases. Ann Periodontol. 1999;4:78.
14. Papapanou PN, Sanz M, et al. Periodontitis: Consensus report of
workgroup 2 of the 2017 World Workshop on the Classification
of Periodontal and Peri‐Implant Diseases and Conditions. J Clin
Periodontol. 2018;45(Suppl 20):S162–S170.
15. Herrera D, Retamal‐Valdes B, Alonso B, Feres M. Acute periodontal
lesions (periodontal abscesses and necrotizing periodontal diseases)
and endo‐periodontal lesions. J Clin Periodontol. 2018;45(Suppl
20):S78–S94.
CO N C LU S I O N S
16. Albandar JM, Susin C, Hughes FJ. Manifestations of systemic
diseases and conditions that affect the periodontal attachment
This overview introduces an updated classification of periodontal dis‐ apparatus: case definitions and diagnostic considerations. J Clin
eases and conditions and a new classification of peri‐implant diseases Periodontol. 2018;45(Suppl 20):S171–S189.
17. Needleman I, Garcia R, Gkranias N, et al. Mean annual attachment,
and conditions. The publication represents the work of the worldwide
bone level and tooth loss: A systematic review. J Clin Periodontol.
community of scholars and clinicians in periodontology and implant 2018;45(Suppl 20):S112–S129.
dentistry. This paper presents an abbreviated overview of the outcome 18. Fine DH, Patil AG, Loos BG. Classification and diagnosis of ag‐
of the consensus workshop, and the reader is encouraged to review gressive periodontitis. J Clin Periodontol. 2018;45(Suppl 20):
the entire publication to receive comprehensive information about the S95–S111.
19. Billings M, Holtfreter B, Papapanou PN, Mitnik GL, Kocher T, Dye
rationale, criteria and implementation of the new classifications.
BA. Age‐dependent distribution of periodontitis in two countries:
findings from NHANES 2009 to 2014 and SHIP‐TREND 2008 to
2012. J Clin Periodontol. 2018;45(Suppl 20):S130–S148.
AC K N OW L E D G M E N T S A N D D I S C LO S U R E S 20. Tonetti MS, Greenwell H, Kornman KS. Staging and grading of peri‐
odontitis: Framework and proposal of a new classification and case
The authors filed detailed disclosure of potential conflicts of in‐
definition. J Clin Periodontol. 2018;45(Suppl 20):S149–S161.
terest relevant to the workshop topics, and these are kept on file. 21. Jepsen S, Caton JG, et al. Periodontal manifestations of systemic
Additional disclosures can be found in each of the four consensus diseases and developmental and acquired conditions: consen‐
reports published in these proceedings. sus report of workgroup 3 of the 2017 World Workshop on the
Conditions. J Clin Periodontol. 2018;45(Suppl 20):S219–S229.
REFERENCES 22. Sanz M, Ceriello A, Buysschaert M, et al. Scientific evidence on the
links between periodontal diseases and diabetes: consensus report
1. Armitage GC. Development of a classification system for periodon‐ and guidelines of the joint workshop on periodontal diseases and di‐
tal diseases and conditions. Ann Periodontol. 1999;4:1–6. abetes by the International Diabetes Federation and the European
2. Lang NP, Bartold PM. Periodontal health. J Clin Periodontol. Federation of Periodontology. J Clin Periodontol. 2018;45:138–149.
2018;45(Suppl 20):S230–S236. 23. Cortellini P, Bissada NF. Mucogingival conditions in the natural den‐
3. Murakami S, Mealey BL, Mariotti A, Chapple ILC. Dental plaque‐ tition: Narrative review, case definitions, and diagnostic consider‐
induced gingival conditions. J Clin Periodontol. 2018;45(Suppl ations. J Clin Periodontol. 2018;45(Suppl 20):S199–S206.
20):S17–S27. 24. Fan J, Caton JG. Occlusal trauma and excessive occlusal forces:
4. Holmstrup P, Plemons J, Meyle J. Non–plaque‐induced gingival dis‐ Narrative review, case definitions, and diagnostic considerations. J
eases. J Clin Periodontol. 2018;45(Suppl 20):S28–S43. Clin Periodontol. 2018;45(Suppl 20):S207–S218.
5. Trombelli L, Farina R, Silva CO, Tatakis DN. Plaque‐induced gingivi‐ 25. Ercoli C, Caton JG. Dental prostheses and tooth‐related factors. J
tis: Case definition and diagnostic considerations. J Clin Periodontol. Clin Periodontol. 2018;45(Suppl 20):S207–S218.
2018;45(Suppl 20):S44–S66. 26. Berglundh T, Armitage G, et al. Peri‐implant diseases and conditions:
6. Chapple ILC, Mealey BL, et al. Periodontal health and gingival dis‐ Consensus report of workgroup 4 of the 2017 World Workshop
eases and conditions on an intact and a reduced periodontium: on the Classification of Periodontal and Peri‐Implant Diseases and
consensus report of workgroup 1 of the 2017 World Workshop Conditions. J Clin Periodontol. 2018;45(Suppl 20):S286–S291.
on the Classification of Periodontal and Peri‐Implant Diseases and 27. Araujo MG, Lindhe J. Peri‐implant health. J Clin Periodontol.
Conditions. J Clin Periodontol. 2018;45(Suppl 20):S68–S77. 2018;45(Suppl 20):S36–S36.
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28. Heitz‐Mayfield LJA, Salvi GE. Peri‐implant mucositis. J Clin

Periodontol. 2018;45(Suppl 20):S237–S245. How to cite this article: Caton J, Armitage G, Berglundh T, et
29. Schwarz F, Derks J, Monje A, Wang H‐L. Peri‐implantitis. J Clin
al. A new classification scheme for periodontal and peri‐
Periodontol. 2018;45(Suppl 20):S246–S266.
30. Renvert S, Persson GR, Pirih FQ, Camargo PM. Peri‐implant
implant diseases and conditions – Introduction and key
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and diagnostic considerations. J Clin Periodontol. 2018;45(Suppl 2018;45(Suppl 20):S1–S8. https://doi.org/10.1111/jcpe.12935
20):S278–S285.
31. Hämmerle CHF, Tarnow D. The etiology of hard‐ and soft‐tissue de‐
ficiencies at dental implants: A narrative review. J Clin Periodontol.
2018;45(Suppl 20):S267–S277.
Received: 9 March 2017 | Revised: 4 September 2017 | Accepted: 13 September 2017
DOI: 10.1111/jcpe.12938
2017 WORLD WORKSHOP
Non–plaque‐induced gingival diseases
Palle Holmstrup1 | Jacqueline Plemons2 | Joerg Meyle3
1
Section of Periodontology, Department of
Odontology, Faculty of Health and Medical Abstract
Sciences, University of Copenhagen, While plaque‐induced gingivitis is one of the most common human inflammatory dis‐
Copenhagen, Denmark
2
eases, several non–plaque‐induced gingival diseases are less common but often of
Department of Periodontics, Texas A&M
University College of Dentistry, Dallas, TX, major significance for patients. The non–plaque‐induced gingival lesions are often
USA
manifestations of systemic conditions, but they may also represent pathologic
3
Department of Periodontology, University
changes limited to gingival tissues. A classification is proposed, based on the etiology
of Giessen, Giessen, Germany
of the lesions and includes: Genetic/Developmental disorders; Specific infections;
Correspondence
Inflammatory and immune conditions and lesions; Reactive processes; Neoplasms;
Prof. Palle Holmstrup, Section of
Periodontology, Department of Odontology, Endocrine, Nutritional and metabolic diseases; Traumatic lesions; and Gingival
Faculty of Health and Medical Sciences,
pigmentation.
University of Copenhagen, 20 Noerre Allé,
DK‐2200 Copenhagen, Denmark.
Email: [email protected] KEYWORDS
classification, diagnosis oral, epulis, gingiva, gingival diseases, immunological, inflammation,
mouth mucosa, oral manifestations, oral medicine, periodontal disease, rare diseases
the Journal of Periodontology and Journal of
Human gingiva as well as other oral tissues may exhibit several non– and to discuss briefly the more common of these. The major differ‐
plaque‐induced pathologic lesions, which may in some instances be ence between the present classification proposal and that of the
manifestations of a systemic condition or a medical disorder. They may 1999 workshop is creation of a more comprehensive nomenclature
also represent pathologic changes limited to gingival tissues. Although and inclusion of ICD‐10 diagnostic codes. Because some of the con‐
these lesions are not directly caused by plaque, their clinical course ditions seldom manifest in the oral cavity and some even more sel‐
may be impacted by plaque accumulation and subsequent gingival in‐ dom present gingival manifestations, detailed appraisal is included
flammation. Dentists are the key healthcare providers in establishing within Table 2.
diagnoses and formulating treatment plans for patients affected by
such lesions. Specialists in periodontology should be familiar with and
D E S C R I P TI O N O F S E LEC TE D D I S E A S E
be able to diagnose, treat, or refer for treatment any such lesion.
E NTITI E S :
A review of non–plaque‐induced gingival lesions was pre‐
sented at the 1999 International Workshop for a Classification of
1 | G E N E TI C/D E V E LO PM E NTA L
Periodontal Diseases and Conditions,1 and the present review aims
A B N O R M A LITI E S
to add available additional literature as well as diseases and condi‐
tions which were not included in the former review. Several of the
1.1 | Hereditary gingival fibromatosis (HGF)
diseases and their treatment have been reviewed recently. 2‒4 The
purpose of the current review is not to repeat the details of such Clinically, gingival fibromatosis may present gingival overgrowth in
texts, but to present a contemporary classification of the most rele‐ various degrees. Compared to drug‐related gingival overgrowth, he‐
vant non–plaque‐induced gingival diseases and conditions (Table 1) reditary gingival fibromatosis is a rare disease which may occur as

HOLMSTRUP et al. | S29
TA B L E 1 Classification table summary: non–plaque‐induced an isolated disease or as part of a syndrome. It has a genetic basis in
gingival diseases and conditions mutations of the Son of Sevenless gene5 (see Table 2).
1 Genetic/developmental disorders
1.1 Hereditary gingival fibromatosis (HGF)
2 Specific infections 2 | S PEC I FI C I N FEC TI O N S
2.1 Bacterial origin
Necrotizing periodontal diseases (Treponema spp., Selenomonas spp.,
Fusobacterium spp., Prevotella intermedia, and others) 2.1 | Bacterial origin
Neisseria gonorrhoeae (gonorrhea)
Treponema pallidum (syphilis)
Mycobacterium tuberculosis (tuberculosis)
Necrotizing periodontal disease
Streptococcal gingivitis (strains of streptococcus)
2.2 Viral origin Necrotizing gingivitis (NG), necrotizing periodontitis (NP), and
Coxsackie virus (hand‐foot‐and‐mouth disease) necrotizing stomatitis (NS) are severe inflammatory periodontal
Herpes simplex 1/2 (primary or recurrent)
diseases caused by bacterial infection in patients with specific un‐
Varicella‐zoster virus (chicken pox or shingles affecting V nerve)
Molluscum contagiosum virus derlying risk factors (poor oral hygiene, smoking, stress, poor nutri‐
Human papilloma virus (squamous cell papilloma, condyloma tion, compromised immune status [e.g., HIV]).
acuminatum, verrucca vulgaris, and focal epithelial hyperplasia)
2.3 Fungal Although the necrotizing diseases often run an acute, rapidly de‐
Candidosis structive course, the term acute has not been included in the diag‐
Other mycoses (e.g., histoplasmosis, aspergillosis)
noses since 1999. Since superficial necrosis always involves an ulcer,
3 Inflammatory and immune conditions and lesions
3.1 Hypersensitivity reactions it is requested to delete the term “ulcerative.” The term “gingivitis”
Contact allergy is used for lesions only involving gingival tissue and characterized by
Plasma cell gingivitis
Erythema multiforme no loss of periodontal attachment.6 Central necrosis of the papillae
3.2 Autoimmune diseases of skin and mucous membranes may result in considerable tissue destruction with formation of a cra‐
Pemphigus vulgaris
ter. If loss of attachment is established, the diagnosis consequently
Pemphigoid
Lichen planus becomes NP.7 For lesions with ulceration extending >1.0 cm from the
Lupus erythematosus gingival margin, including tissue beyond the mucogingival junction,
3.3. Granulomatous inflammatory conditions (orofacial granulomatosis)
Crohn's disease the term NS has been used.8 The three necrotizing diseases appear
Sarcoidosis to represent various stages of the same disease process,9 and a dis‐
4 Reactive processes
tinction between the different manifestations has not always been
4.1 Epulides
Fibrous epulis made in the literature. As a result, the term “necrotizing periodontal
Calcifying fibroblastic granuloma disease” (NPD) is proposed as a common term encompassing NG,
Pyogenic granuloma (vascular epulis)
Peripheral giant cell granuloma (or central) NP, and NS. Further details are presented in Table 2. A constant and
5 Neoplasms variable part of the microflora in NPD lesions have been described.
5.1 Premalignant
The constant flora primarily contains Treponema spp., Selenomonas
Leukoplakia
Erythroplakia spp., Fusobacterium spp., and Prevotella intermedia; the variable flora
5.2 Malignant consists of a heterogeneous array of bacterial types.10,11
Squamous cell carcinoma
Leukemia
Lymphoma
6 Endocrine, nutritional, and metabolic diseases Other bacterial infections
6.1 Vitamin deficiencies
Vitamin C deficiency (scurvy) Non–plaque‐associated bacterial infections of the gingiva are un‐
7 Traumatic lesions common. Gingivitis caused by a specific bacterial infection may,
7.1 Physical/mechanical insults
Frictional keratosis
however, arise due to a loss of homeostasis between non–plaque‐
Toothbrushing‐induced gingival ulceration related pathogens and innate host resistance.12 Acute streptococcal
Factitious injury (self‐harm)
gingivitis is an example of a rare acute non–plaque‐associated gin‐
7.2 Chemical (toxic) insults
Etching gival inflammation.13‒15 Other examples of specific bacterial infec‐
Chlorhexidine tions of the gingiva may also be due to Neisseria gonorrhoeae16,17 and
Acetylsalicylic acid
Cocaine
Treponema pallidum.12,16‒18 Orofacial tuberculosis is a rare manifes‐
Hydrogen peroxide tation of extrapulmonary tuberculosis, occurring in approximately
Dentifrice detergents
0.1% to 5% of all tuberculosis infections.19
Paraformaldehyde or calcium hydroxide
7.3 Thermal insults
Burns of mucosa
8 Gingival pigmentation 2.2 | Viral origin
Gingival pigmentation/melanoplakia
Smoker's melanosis The most important viruses to cause gingival manifestations are
Drug‐induced pigmentation (antimalarials; minocycline)
Coxsackie viruses and the herpes viruses including herpes simplex
Amalgam tattoo
virus types 1 (HSV‐1) and 2 (HSV‐2) and varicella‐zoster virus. 20
S30 | HOLMSTRUP et al.
Although these viruses most often infect individuals in childhood, skin. In adults, the disease appears in the genital areas and is often
primary infections may occur in adult life as well. They may give rise sexually transmitted.
to oral mucosal disease followed by periods of latency and some‐
times reactivation.
Human papilloma virus (HPV)
More than 100 types of HPV have been identified, and at least the
Coxsackie viruses
following 25 types have been detected in oral lesions: 1, 2, 3, 4, 6, 7,
Coxsackie viruses may cause herpangina and hand‐foot‐and‐mouth 10, 11, 13, 16, 18, 31, 32, 33, 35, 40, 45, 52, 55, 57, 58, 59, 69, 72, 73.
disease (synonym: vesicular stomatitis with exanthema). While her‐ The benign oral lesions, associated with HPV infection, include squa‐
pangina does not involve gingiva, hand‐foot‐and‐mouth disease is a mous cell papilloma, condyloma acuminatum, verruca vulgaris, and
common contagious vesicular viral disease affecting skin and oral mu‐ focal epithelial hyperplasia, and they appear to be associated with
cosa including gingiva. The lesions are primarily seen in children and different distinct HPV subtypes. Oral benign HPV lesions are mostly
mainly caused by coxsackie viruses A6, A10, and A16 (see Table 2).21 asymptomatic, and may persist or regress spontaneously (Table 2).31
HSV‐1 and HSV‐2 2.3 | Fungal origin

HSV‐1 usually causes oral manifestations, in contrast to HSV‐2, A number of fungi may give rise to oral infections, including candido‐
which is primarily involved in anogenital infections and only occa‐ sis, histoplasmosis, aspergillosis, blastomycosis, coccidioidomycosis,
sionally in oral infections. 20 paracoccidioidomycosis, cryptococcosis, geotricosis, mucormyco‐
sis.32 Several of these are uncommon, and oral manifestations may
more likely occur with immune deterioration.33,34 Oral mycoses can
Herpetic gingivostomatitis
cause acute, chronic, and mucocutaneous lesions.35 Candidosis is
Primary herpetic infection typically occurs in infants and has an incu‐ the most common mouth mycosis, while histoplasmosis and asper‐
bation period of 1 week. It may run an asymptomatic course in early gillosis are less common (Table 2).
childhood, but it may also give rise to gingivostomatitis with severe
manifestations. A characteristic feature is the formation of few or
Candidosis
many vesicles, which rupture, coalesce, and leave fibrin‐coated ul‐
cers often of irregular extension (Table 2). 20,22 Several candida species may be isolated from the mouth of humans, in‐
Recurrent intraoral herpes simplex lesions typically occur in adults cluding C. albicans, C. glabrata, C. krusei, C. tropicalis, C. parapsilosis, and
and have a much less dramatic course (Table 2). As a result, they C. guillermondii. The most common fungal infection of the oral mucosa
may remain undiagnosed or mistaken for aphthous ulcerations23,24 is candidosis mainly caused by C. albicans. C. albicans is a normal com‐
despite the fact that aphthous ulcers do not typically affect kerati‐ mensal organism of the oral cavity but also an opportunistic pathogen.36
23
nized mucosa. While candidal infection can be seen anywhere in the oral mucosa, le‐
sions of the gingiva are seldom seen in otherwise healthy individuals.
The most common clinical characteristic of gingival candidal infection is
Varicella‐zoster virus
redness of the attached gingiva, often with a granular surface.
The primary infection of varicella‐zoster virus causes varicella (chicken Nodular gingival lesions are uncommon and are characterized
pox), which occurs mainly in children (Table 2). Later reactivation of the by slightly elevated nodules of a white or reddish color.37 Diagnosis
virus in adults causes herpes zoster (shingles) with unilateral lesions of candidal infection can be accomplished on the basis of culture,
following the distribution of an infected nerve. If the second or third smear, and biopsy. “Linear gingival erythema” described in the 1999
branch of the trigeminal nerve is involved, skin lesions may be associ‐ International Workshop, sometimes associated with HIV infection,
25,26
ated with intraoral lesions, including gingival lesions, and intraoral is now generally regarded as gingival candidosis and has therefore
lesions may occur alone.26 Initial symptoms are pain and paresthesia, been removed from this classification.
which may be present before lesions appear.27 The initial lesions are
vesicles, which soon rupture and leave fibrin‐coated small ulcers, often
3 | I N FL A M M ATO RY A N D I M M U N E
coalescing to irregular forms (Table 2).28
CO N D ITI O N S A N D LE S I O N S
Molluscum contagiosum virus 3.1 | Hypersensitivity reactions

Molluscum contagiosum virus of the poxvirus family causes mollus‐
Contact allergy
cum contagiosum, which is a contagious disease with infrequent oral
manifestations (Table 2). 29,30 It is seen in infants with immature im‐ Oral mucosal manifestations of hypersensitivity (allergy) are very
mune systems and manifests as discrete umbilicated papules on the uncommon. As mentioned in the 1999 classification review,1 such
TA B L E 2 Features of the more common non–plaque‐induced gingival lesions and conditions
Subheading and diagnosis ICD‐10 code Clinical presentation Etiology Associated conditions Diagnostic investigations
1. Genetic/developmental disorders
HOLMSTRUP et al.
1.1. Hereditary gingival K06.1 Generalized fibrous gingival enlarge‐ Mutation localized to 2p21‐p22 N/A Excisional biopsy for histopathology
fibromatosis ment of tuberosities, anterior free/ (HGF1) & 5q13‐q22 (HGF2)
attached gingiva and retro‐molar pads Mutations of “Son of Sevenless”
genes (SOS 1, SOS2)119
2. Specific infections
2.1. Bacterial origin
Necrotizing periodontal diseases A69.0 Ulceration with central necrosis of the Treponema spp., Selenomonas spp., Poor oral hygiene, Characteristic clinical features
papillae may result in considerable Fusobacterium spp., and smoking, stress, poor
tissue destruction with formation of a Prevotella intermedia and nutrition, immune
crater7,8 others10,11 compromise e.g. HIV
Gonorrhea A54.8 Unspecific lesions with ulcers or fiery Neisseria gonorrhoeae May be associated with Microbiological identification of
red mucosa and white pseudomem‐ painful pharyngitis and pathogen
brane with or without symptoms120 lymphadenopathy.
Genital infection of
sexual partner.
Syphilis A51.2 Fiery red, edematous and often painful Treponema pallidum Clinical features combined with
ulcerations, asymptomatic chancres or dark‐field examination of smear.
mucous patches, or atypical non‐ulcer‐ Serologic reactions are present
ated, inflamed gingivitis after few weeks.
Tuberculosis A18.8 Nodular or papillary proliferation of Mycobacterium tuberculosis Most often combined with Biopsy demonstrating granulomas
inflamed gingival tissues19 pulmonary infection with multinucleated giant cells
Streptococcal gingivitis K05.01 Acute gingivitis not associated with Strains of streptococcus Sometimes preceded by Biopsy combined with microbiologic
plaque upper respiratory examination
infection
2.2. Viral origin
Hand‐foot‐and‐mouth disease Small vesicles that after rupture leave Coxsackie virus A 6, A 10 and A Similar skin lesions of Clinical features with lesions of skin
fibrinous coated ulcers. Usually in 16 hands and feet; and oral mucosa
children sometimes fever
Primary herpetic B00.2 Gingivostomatitis with severe Herpes simplex virus types 1 and Lymphadenitis, eventually Few or many vesicles, which rupture,
gingivostomatitis manifestations including painful 2 fever coalesce, and leave fibrin‐coated
gingivitis, ulcerations, edema and ulcers often of irregular extension
stomatitis
Recurrent intraoral herpes B00 Cluster of small painful ulcers in Herpes simplex virus types 1 and Characteristic lesions combined with
simplex attached gingiva and hard palate23 2 patient history
Chicken pox (varicella) B01.8 Usually affecting children: small Varicella‐zoster virus Fever, malaise, and a skin Clinical features
yellowish vesicles which rapidly rash
|
rupture
(Continues)
S31
S32
TA B L E 2 (continued)
|
Shingles (herpes zoster) B02 Unilateral painful ulcers preceded by Varicella‐ zoster virus Sometimes combined with Affecting second or third branch of
vesicles. Lesions coalesce to form skin lesions trigeminal nerve
irregular ulcers. 28
Molluscum contagiosum virus B08.1 Molluscum contagiosum is a skin and Molluscum contagiosum virus, Discrete umbilicated Clinical features
mucosal disease of viral origin with which is a virus of the poxvirus papules on the skin of
infrequent oral mucosal involvement30 family face and29 trunk or in
adults, in the genital
areas due to sexual
transmission
Squamous cell papilloma, B07.8 Asymptomatic exophytic papillomato‐ Human papilloma virus (HPV) Histopathology of removed lesion
condyloma acuminatum, sis, verrucous or flat lesions31
verrucca vulgaris and focal
epithelial hyperplasia
2.3. Fungal
Candidosis B37 Various types of clinical manifestations Various Candida‐species, most Sometimes oral involve‐ Definitive diagnosis is confirmed
including: commonly Candida albicans ment is secondary to a with histologic review of biopsied
• pseudomembranous (also known as more serious systemic tissue as well as pertinent culture
thrush in neonates) infection results
• erythematous
• plaque‐like
• nodular37
Histoplasmosis B39 Nodular, papillary or granulomatous Histoplasma capsulatum Clinical features, histopathologic
lesions, which develop loss of tissue examination and/or culture
with ulcerations and pain32
Aspergillosis B44 Early stage characterized by violaceous Aspergillus spp. Oral involvement is Clinical features, histopathologic
marginal gingiva. More advanced commonly secondary to examination and/or culture34
lesions become necrotic and covered more serious systemic
by a pseudomembrane containing infection33. In the late
fungal hyphae. stage, the lesions may
progress and include
destruction of the
alveolar bone and
surrounding facial
muscles.
3. Inflammatory and immune conditions and lesions
3.1. Hypersensitivity reactions
Contact allergy K08.55/ Redness and sometimes lichenoid Type IV hypersensitivity to dental Histopathology shows chronic
Z91.01/ lesions restorative materials, dentifrices, inflammatory reaction often
Z91.04 mouthwashes and foods lichenoid infiltration of primarily
lymphocytes
(Continues)
HOLMSTRUP et al.
Plasma cell gingivitis C90 Erythematous gingiva with a velvety Histopathology reveals dense
texture usually affecting the anterior infiltrate of plasma cells in lamina
maxillary gingiva39 propria.121 Allergen to be identified
HOLMSTRUP et al.
by dermatologist.
Erythema multiforme L51 The manifestations are varied, the most May be associated with Clinical manifestations combined
characteristic having a rounded shape skin lesions usually with patient history and biopsy
with a central red area, a paler pink or appearing symmetrically
edematous zone, and a red periphery. on the distal extremities
May also present only with erythema, and progressing
erosions and ulcers. proximally
3.2. Autoimmune diseases of skin and mucous membranes
Pemphigus vulgaris L10 Gingival manifestation is usually The intraepithelial bullae in skin Bullous lesions of the skin Diagnosis is based on clinical
described as desquamative gingivitis and mucous membranes are due are common presentation and confirmed by
and/or as vesiculo‐bullous lesions of to formation of autoantibodies histopathology and the presence of
the free and attached gingiva directed against desmosome‐as‐ circulating autoantibody titers to
characterized by intraepithelial bullae sociated protein antigens desmoglein 1 and 3 which can be
which, after rupture, leave (desmoglein‐3) residing in detected by enzyme‐linked
erosions 42,62 epithelial and epidermal immunosorbent assay
intercellular substance
Pemphigoid L12.1 Desquamative lesions of the gingiva Caused by autoantibodies towards Scarring is a serious Clinical features and histopathology.
presenting as intensely erythematous hemidesmosome or lamina lucida concern for ocular lesions Circulating antibodies are not
areas. Rubbing of gingiva may components resulting in always found by indirect
precipitate bulla formation, which is detachment of the epithelium immunofluorescence.
called a positive Nicholsky sign and is from the connective tissue in the
caused by the destroyed adhesion of basement membrane zone
the epithelium to the connective tissue.
Lichen planus L43.8 Papular, reticular, plaque type, Inflammatory reaction towards an Presence of papular or reticular
erythematous (atrophic), ulcerative unidentified antigen in the basal lesions are characteristic of lichen
(erosive) or bullous lesions55 epithelial layer/basement planus. Diagnosis based on clinical
membrane zone features and histopathology49
Lupus erythematosus (LE) L93 The typical lesion presents as a central Deposits of antigen–‐antibody The dark‐red “butterfly” Clinical features and histopathologi‐
atrophic area with small white dots complexes appear to play a role skin lesions are photo‐ cal findings
surrounded by irradiating fine white in the tissue damage characteris‐ sensitive, scaly,
striae. Ulcerations may be a sign of tic of the disease122 erythematous macules
systemic LE. 57,59 located on the bridge of
the nose and the
cheeks60
3.3 Granulomatous inflammatory conditions (orofacial granulomatosis)
Crohn's disease K50 Cobblestone appearance of the oral Granuloma in the soft tissue of General complications, Clinical and histopathological
mucosa, linear ulceration and gingival the oral cavity or the intestinal intestinal pain, anal findings
|
overgrowth60 soft tissue fissures, diarrhea. Labial

enlargement is common.
S33
(Continues)
S34
|
Sarcoidosis D86.8 Gingival swelling, nodules, ulcerations Granuloma in the soft tissue of Clinical and histopathological
and gingival recession, loosening of the oral cavity or in the intestinal findings
teeth and swelling of salivary glands soft tissue
4. Reactive processes
4.1 Epulides
Fibrous epulis K06.8 Exophytic smooth‐surfaced pink Presumably the result of Clinical and histopathologic features
masses of fibrous consistency continued physical trauma 65,66
attached to the gingiva65,66
Calcifying fibroblastic granuloma L92.8 Pedunculated or sessile red to pink Clinical and histopathologic features
mass usually derived from the
interdental papilla
Pyogenic granuloma (vascular L98 Ulcerated, smooth or lobulated Clinical and histopathologic features
epulis) pedunculated or sessile mass, red to
pink in color depending on the
duration of the lesion
Peripheral giant cell granuloma M27.1 Well‐defined, sessile or pedunculated Clinical and histopathologic features
(or central) soft tumor‐like process with a purple,
sometimes bluish to brownish
color123,124
5. Neoplasms
5.1 Premalignant
Leukoplakia K13.21 Not‐removable white spot in the oral Tobacco and alcohol usage may be Clinical and histopathologic features
mucosa with smooth, corrugated or involved ruling out other diagnoses
verrucous surface72,73
Erythroplakia K13.29 Red, often sharply demarcated with the May be associated with oral lichen Clinical and histopathologic features
surface below the surrounding mucosa planus125 ruling out other diagnoses.
5.2 Malignant
Squamous cell carcinoma 44.02 Gingival squamous cell carcinoma often Tobacco and alcohol usage may be Clinical and histopathologic features
presents as painless exophytic masses, involved in the pathogenesis
red and white speckled patches or
non‐healing ulcerations involving the
keratinized gingiva
Leukemia C95 Various changes including pallor of the Immunosuppression due to Dysphagia, facial paralysis, Differential blood cell analysis of the
oral mucosa, pain, petechiae and malignant transformation of and paresthesia of the venous blood, bone marrow biopsy
ecchymosis, gingival bleeding and leukocyte production in the bone face, lips, tongue and
gingival swelling due to leukemic cell marrow chin, and trismus may
infiltration.82‒84 Deep punched‐out occur
ulcerations and necrosis on gingiva
and tooth mobility.126,127
(Continues)
HOLMSTRUP et al.
HOLMSTRUP et al.
Lymphoma C85.91 Non‐specific gingival swelling may be Hodgkin lymphoma is associated Swelling of lymph nodes Histopathology of biopsy
the first manifestation of non‐Hodgkin with Epstein‐barr virus and an
lymphoma, mimicking a periodontal increased incidence is seen in
abscess or pyogenic granuloma128‒130 immunocompromised
patients131,132
6. Endocrine, nutritional and metabolic diseases
6.1. Vitamin deficiencies
Vitamin C deficiency (Scurvy) E64.2 Enhanced gingival bleeding, ulceration, Changes in connective tissue Malaise Reduced plasma ascorbic acid
swelling metabolism due to lack of concentration
ascorbic acid
7. Traumatic lesions
7.1. Physical/mechanical insults
Frictional keratosis K13.29 White lesion sharply demarcated, Limited trauma often due to Clinical and histopathological
leukoplakia‐like asymptomatic, inappropriate toothbrushing features
homogeneous whitish‐plaques that are
irremovable usually presenting on
facial attached gingiva92
Toothbrushing‐induced gingival K05.10 Superficial, often horizontal gingival Excessive trauma, due to Clinical findings
ulceration laceration to major loss of tissue often inappropriate toothbrushing
resulting in gingival recession93,94
Factitious injury (self‐harm) F68.1 Unusual tissue damage with ulceration Pressure from fingernails, Clinical findings combined with
in areas that can easily be reached by application of pencils, pocket patient history
fingers and instruments91 knives or other types of
instruments91
7.2. Chemical (toxic) insults
Etching, chlorhexidine, L43.8 Surface slough or ulceration May be related to patient's use of Clinical findings combined with
acetylsalicylic acid, cocaine, chlorhexidine,97,98 acetylsalicylic patient history
hydrogen peroxide, dentifrice acid,99,100 cocaine,101 hydrogen
detergents, paraformaldehyde peroxide,102,103 dentifrice
or calcium hydroxide detergents,104 paraformaldehyde
or calcium hydroxide
7.3. Thermal insults
Burns of mucosa K13.7 Erythematous lesions that may slough a Clinical findings combined with
coagulated surface. Vesicles and patient history
sometimes ulceration, petecchia or
erosion.108
(Continues)
|
S35
S36
|
8. Gingival pigmentation
Gingival pigmentation/ L81.9 Brownish to black diffusely pigmented Most often physiologic pigmenta‐ Sometimes combined with Clinical findings eventually
melanoplakia areas tion in persons with a dark skin endocrine disturbances combined with laboratory
complexion (Addison's disease), investigation
syndromes (Albright
syndrome, Peutz Jegher
syndrome)
Smoker's melanosis K13.24 Brownish areas most often on Deposits of melanin synthesized Clinical findings in smokers
mandibular facial gingiva111,112 due to influence of smoking
Drug‐induced pigmentation L83 Bluish grey or brownish to black diffuse Accumulation of melanin, deposits Clinical finding combined with
(antimalarials, minocycline) pigmentation of drug or drug metabolites, or patient history
synthesis of pigments under the
influence of a drug or deposition
of iron following damage to the
vessels
Amalgam tattoo L81.8 Usually small bluish or grey to black Accumulation of amalgam Clinical findings eventually
localized pigmentation, which is not fragments or small amalgam combined with radiographs to
elevated particles. May be result of identify larger fragments. In cases
fracture of amalgam filling during where amalgam tattoo cannot be
extraction or due to small differentiated from other causes of
particles of amalgam being oral pigmentation, a biopsy may be
spilled into wounds during performed.118
restorative procedures.
HOLMSTRUP et al.
reactions may be due to dental restorative materials, dentifrices, connective tissue at the basement membrane area is the main di‐
mouthwashes, and foods and are most often type IV hypersensitiv‐ agnostic feature of MMP, and circulating serum antibodies are not
ity reactions (contact allergy). always revealed by indirect immunofluorescence.48
Plasma cell gingivitis Lichen planus

Plasma cell gingivitis is an uncommon inflammatory condition usu‐ Lichen planus is a common mucocutaneous disease with frequent
ally affecting the anterior maxillary gingiva and of uncertain etiology. manifestation on the gingiva. Oral involvement alone is common,
While some authors have associated plasma cell gingivitis with a hy‐ and concomitant skin lesions in patients with oral lesions have been
38
persensitivity response to antigens in various substances, others found in 5% to 44% of the cases.49,50 The major characteristic of
have raised doubt whether plasma cell gingivitis is a distinct clinico‐ this disease is an inflammatory reaction toward an unidentified an‐
pathologic entity.39 tigen in the basal epithelial layer/basement membrane zone. The
disease may be associated with severe discomfort. Because it has
been shown to possess a premalignant potential, 51‒53 it is important
Erythema multiforme (EM)
to diagnose, treat, and follow patients through regular oral examina‐
EM is an uncommon, self‐limiting, acute immune‐inflammatory dis‐ tions.51,52,54 Six types of clinical manifestation have been described
order of the oral mucosa (Table 2). The etiology of EM is unclear in (Table 2).55 The lesions, usually bilateral, often involve the gingiva
most patients, but it appears to be an immunologic hypersensitivity and present as desquamative gingivitis causing pain and discomfort
reaction mediated by T‐lymphocytes. The disorder may present a during eating and toothbrushing. The clinical diagnosis is based on
diagnostic dilemma because infections (particularly, herpes simplex the presence of papular‐ or reticular‐ type lesions, eventually sup‐
and mycoplasma pneumoniae) and some drugs seem to predispose ported by histopathologic findings of hyperkeratosis, degenerative
toward the development of erythema multiforme, in what are be‐ changes of basal cells, and subepithelial inflammation dominated by
lieved to be immune complex disorders.40 lymphocytes and macrophages.49 In a recent randomized controlled
trial, a tailored plaque‐control regime was shown to be beneficial in
reducing symptoms of gingival lichen planus and improving overall
3.2 | Autoimmune diseases of skin and
quality of life.56
mucous membranes
Pemphigus vulgaris (PV) Lupus erythematosus (LE)

PV is an autoimmune vesiculo‐bullous disease of skin and mucous LE is a group of autoimmune disorders characterized by autoanti‐
membranes. Involvement of the oral mucosa is common, and in bodies to various cellular constituents, including extractable nu‐
about 54% of cases, the oral cavity has been reported to be the pri‐ clear antigens and cytoplasmic membrane components. Two major
mary site of involvement.41 The disease is characterized by intraepi‐ forms are described: discoid LE (DLE) and systemic LE (SLE), which
thelial bullae in skin and mucous membranes due to auto‐antibodies may involve a range of organ systems. DLE is a mild chronic form,
directed against desmosome‐associated protein antigens (desmo‐ which involves skin and mucous membranes, sometimes including
glein‐3). Oral mucosal lesions, including gingival lesions, may pre‐ the gingiva as well as other parts of the oral mucosa. 57,58 The typi‐
42
cede skin involvement. In the literature, gingival localization of PV cal lesion presents as a central atrophic area with small white dots
usually manifests as desquamative gingivitis and/or as vesiculo‐bul‐ surrounded by irradiating fine white striae (Table 2). Eight percent
lous lesions of the free and attached gingiva; early lesions only rarely of patients with DLE develop SLE, and ulcerations may be a sign
appear as extensive erythema and erosions (Table 2).43 of SLE. 57,59 The characteristic dark red “butterfly” skin lesions are
photosensitive, scaly, erythematous macules located on the bridge
of the nose and the cheeks.60 The systemic type may also include
Pemphigoid
skin lesions located on the face, but they tend to spread over the
Pemphigoid is a group of mucocutaneous disorders caused by au‐ entire body.
toantibodies toward antigens of the basement membrane, result‐
ing in detachment of the epithelium from the connective tissue. If
3.3 | Granulomatous inflammatory conditions
only mucous membranes are affected, the term mucous membrane
(orofacial granulomatosis)
pemphigoid (MMP) is often used.44 Scarring is an important ocular
complication but not for oral mucosal lesions.43 Any area of the oral Persistent enlargement of the soft tissues in the oral cavity as well as
mucosa may be involved in MMP, but the main clinical manifesta‐ the facial region can occur concomitant with various systemic condi‐
tion is desquamative lesions of the gingiva presenting as intensely tions like tuberculosis, Crohn's disease (CD),61 and sarcoidosis. These
45‒47
erythematous areas (Table 2). Usually the bullae rupture rap‐ changes are also seen as a typical symptom of the Melkersson‐
idly, leaving fibrin‐coated ulcers. The separation of epithelium from Rosenthal syndrome (MRS). In 1985, Wiesenfeld introduced the
term orofacial granulomatosis (OFG) to describe granulomas in the

Peripheral giant cell granuloma (or central)
absence of any recognized systemic condition (Table 2).62 The clini‐
cal symptoms of OFG are so similar to CD that OFG may be related Peripheral giant cell granuloma (giant cell epulis, peripheral giant cell
to or may be CD. There is still no consensus whether OFG is a dis‐ reparative granuloma) usually develops from the marginal gingiva.
tinct clinical disorder, or an initial presentation of CD or sarcoidosis, Among 2,068 cases of reactive lesions of the oral cavity, peripheral
or indeed an allergic reaction. 63
giant cell granuloma was the most prevalent lesion (30.12%).64 The
swelling may be sessile or pedunculated, sometimes ulcerated, and
the appearance may resemble pyogenic granulomas (Table 2).69,70
4 | R E AC TI V E PRO C E S S E S
4.1 | Epulides 5 | N EO PL A S M S
Epulis is a term often applied to exophytic processes originating
5.1 | Premalignant
from the gingiva. The term is non‐specific and histopathology is the
basis of a more specific diagnosis. Several of these processes are
Leukoplakia
reactive lesions, i.e., non‐neoplastic proliferations with very similar
clinical appearance to benign neoplastic proliferations.64 Usually The term “leukoplakia” refers to a white lesion of the oral mucosa
there are no symptoms, although the reactive processes are thought that cannot be characterized as any other definable lesion. It is a clin‐
to represent an exaggerated tissue response to limited local irrita‐ ical diagnosis arrived at by exclusion in that all other potential causes
tion or trauma, and they are classified according to their histology. of a white lesion have been ruled out or addressed.71 Lesions are
True epulides include: generally asymptomatic and cannot be rubbed off. Approximately
20% of leukoplakic lesions demonstrate some degree of dysplasia
• Fibrous epulis or carcinoma upon biopsy and most oral cancers are preceded by
• Calcifying fibroblastic granuloma a long‐standing area of leukoplakia. As a result, leukoplakia can be
• Pyogenic granuloma (vascular epulis) considered a premalignant condition. The prevalence of malignant
• Peripheral giant cell granuloma (or central) transformation in leukoplakia ranges from 0.13% to 34%.72 Lesions
occur most frequently on the buccal mucosa, mandibular gingiva,
Among 2,068 cases of reactive lesions of the oral cavity, the at‐ tongue, and floor of the mouth.
tached gingiva with 1,331 (64.36%) cases was the most frequently af‐ Leukoplakia manifests clinically as homogeneous and non‐ho‐
fected location.64 mogenous subtypes. The size of the lesions and clinical features are
determinants of the prognosis.73 Thus, larger lesions and non‐ho‐
mogenous types of lesions imply a greater risk of malignant transfor‐
Fibrous epulis
mation than homogenous leukoplakia.73,74
Fibrous epulides (focal fibrous hyperplasia, irritation fibroma) are Verrucous leukoplakia is characterized by white papillary lesions
common exophytic smooth‐surfaced pink masses of fibrous consist‐ that are covered with a thick keratinized surface. Lesions exhibiting
ency attached to the gingiva. The size varies from small to large tu‐ exophytic growth and invasion of the surrounding tissues are re‐
morlike processes with a diameter of several cm (Table 2).65,66 ferred to as proliferative verrucous leukoplakia, a high‐risk subtype
of non‐homogenous leukoplakia.75
Calcifying fibroblastic granuloma

Erythroplakia
Calcifying fibroblastic granuloma (ossifying fibroid epulis, peripheral
ossifying fibroma) occurs exclusively on the gingiva (Table 2). The Erythroplakia is the red counterpart of leukoplakia in the sense that
lesion, although usually smaller than 1.5 cm in diameter, can reach it is a red lesion, which cannot be diagnosed as any other disease.
a larger size and rarely cause separation of the adjacent teeth and Erythroplakia usually has a higher premalignant potential.76 The le‐
resorption of the alveolar crest. 67,68
sions are uncommon and seldom affect the gingiva (Table 2).73
Pyogenic granuloma 5.2 | Malignant

The pyogenic granuloma (telangiectatic granuloma, pregnancy
Squamous cell carcinoma
granuloma, pregnancy tumor, vascular epulis) is rather common and
shows a striking predilection for the gingiva, which accounts for 75% Squamous cell carcinoma of the gingiva represents about 20%77,78 of
66
of all cases (Table 2). When occurring during pregnancy, the influ‐ intraoral carcinomas and occurs most frequently in the mandibular pre‐
ence of female sex hormones may result in a biologic behavior dis‐ molar and molar regions. Lesions commonly occur in edentulous areas,
tinct from other pyogenic granulomas. but they may also occur at sites in which teeth are present. Mobility of
adjacent teeth is common, and invasion of the underlying alveolar bone Limited physical trauma from brushing may result in gingival hyper‐
is apparent in approximately 50% of cases. Gingival squamous cell car‐ keratosis, a white leukoplakia‐like lesion referred to as frictional
cinoma may mimic other oral lesions affecting the periodontium, most keratosis (Table 2).92
79‒81
of which are reactive or inflammatory in nature.
Toothbrushing‐induced gingival ulceration

Leukemia
In cases of more violent trauma, toothbrushing damage varies from
Leukemias can be classified as acute‐ or chronic‐based on their clini‐ superficial gingival laceration to major loss of tissue resulting in
cal behavior, and lymphocytic/lymphoblastic or myeloid depending on gingival recession (Table 2).93,94 Characteristic findings in these pa‐
their histogenetic origin. Oral lesions occur in both acute and chronic tients are extremely good oral hygiene, cervical tooth abrasion, and
leukemia but are more common in the acute form. The signs and symp‐ unaffected tips of the interdental papillae in the site of injury. The
toms are varied (Table 2). Bacterial, viral, and fungal infections including condition has been termed traumatic ulcerative gingival lesions.93
82‒84
candidosis, and herpes simplex infection may also be present. Inappropriate dental flossing may also cause gingival ulceration and
inflammation primarily affecting the tip of the interdental papillae.
The prevalence of such findings is unknown.95 Diagnosis of the le‐
Lymphoma
sion is based on clinical findings, and an important differential diag‐
Lymphoma is a general term given to tumors of the lymphoid system nosis includes NG.96
and represents the most common hematologic malignancy. Lymphoma
may originate from B‐lymphocyte and T‐lymphocyte cell lines. There
Factitious injury (self‐harm)
are two main types of lymphoma: Hodgkin lymphoma and non‐Hodgkin
lymphoma, the former being one‐sixth as common as non‐Hodgkin Self‐inflicted injury to the gingival tissue is usually seen in young
lymphoma. In contrast to non‐Hodgkin lymphoma (Table 2), oral mani‐ patients, and the lesions may present unusual tissue damage
festations of Hodgkin lymphoma are extremely rare.85‒87 in areas that can easily be reached by fingers and instruments
(Table 2).91
6 | E N D O C R I N E , N U TR ITI O N A L , A N D
M E TA B O LI C D I S E A S E S 7.2 | Chemical (toxic) insults
6.1 | Vitamin deficiencies Etching

Toxic chemical products may result in mucosal surface erosions, in‐
Vitamin C deficiency (scurvy)
cluding reactions of the gingiva. Surface sloughing or ulceration may
Ascorbic acid (vitamin C) is necessary for various metabolic pro‐ be related to the use of chlorhexidine,97,98 acetylsalicylic acid,99,100
cesses in the connective tissue as well as in the formation of cat‐ cocaine,101 hydrogen peroxide,102,103 or to dentifrice detergents.104
echolamines. Clinically, scurvy is characterized by gingival bleeding These lesions are reversible and resolve after removing the toxic
and soreness (Table 2), as well as by a depressed immune response. influence. Injury to the gingival tissue may also be caused by den‐
In gingival health, the concentration of ascorbic acid in gingival crev‐ tists’ incorrect use of substances used for endodontic purposes that
icular fluid is higher than in plasma.88 may be toxic to the gingiva, including paraformaldehyde or calcium
hydroxide, which may give rise to inflammation, ulceration, and ne‐
crosis of the gingival tissue if the cavity sealing is insufficient.105,106
7 | TR AU M ATI C LE S I O N S In most instances, the diagnosis is obvious from the combination of
clinical findings and patient history (Table 2).
Traumatic lesions of the gingiva may be due to a wide range of
causes.89 Such lesions may be self‐inflicted, iatrogenic, or accidental.
7.3 | Thermal insults
Lesions, whether physical, chemical, or thermal in nature, are prob‐
ably among the most common in the mouth, yet the periodontal lit‐ Thermal burns of the gingiva may be prevalent due to a hurried
89‒91
erature contains few references on the topic. lifestyle with intake of microwave‐heated foods and drive‐through
coffee shops.89 Any part of the oral mucosa can be involved, includ‐
ing the gingiva.107 The lesion is erythematous with sloughing of a
7.1 | Physical/mechanical insults
coagulated surface. Vesicles may also occur,108 and sometimes the
lesions present as ulceration, petecchia, or erosions, which may be
Frictional keratosis
painful. The clinical characteristics and the history are important for
Inappropriate toothbrushing can be injurious to the gingival tis‐ the correct diagnosis (Table 2). Gingival injury due to cold has been
sues. Some patients believe they should actively brush the gingiva. described but appears to be very uncommon.109
8 | G I N G I VA L PI G M E NTATI O N 3. Glick M. Burket's Oral Medicine. Shelton, CT: People's Medical

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Received: 29 September 2017 | Revised: 15 October 2017 | Accepted: 21 October 2017
DOI: 10.1111/jcpe.12939
2017 WORLD WORKSHOP
Plaque‐induced gingivitis: Case definition and diagnostic

considerations
Leonardo Trombelli1,2 | Roberto Farina1,2 | Cléverson O. Silva3 | Dimitris N. Tatakis4
1
Research Centre for the Study
of Periodontal and Peri‐Implant Abstract
Diseases, University of Ferrara, Ferrara, Italy Objective: Clinical gingival inflammation is a well‐defined site‐specific condition for
2
Operative Unit of Dentistry, University‐
which several measurement systems have been proposed and validated, and epide‐
Hospital of Ferrara, Ferrara, Italy
3 miological studies consistently indicate its high prevalence globally. However, it is
Department of Dentistry, State University
of Maringá, Maringá, Brazil clear that defining and grading a gingival inflammatory condition at a site level (i.e. a
4
Division of Periodontology, College of “gingivitis site”) is completely different from defining and grading a “gingivitis case”
Dentistry, The Ohio State University,
Columbus, OH, USA (GC) (i.e. a patient affected by gingivitis), and that a “gingivitis site” does not necessar‐
ily mean a “GC”. The purpose of the present review is to summarize the evidence on
Correspondence
Prof. Leonardo Trombelli, Research Center clinical, biochemical, microbiologic, genetic markers as well as symptoms associated
for the Study of Periodontal and Peri‐ with plaque‐induced gingivitis and to propose a set of criteria to define GC.
Implant Diseases, University of Ferrara,
Corso Giovecca 203, 44100 Ferrara, Italy. Importance: A universally accepted case definition for gingivitis would provide the
Email: [email protected] necessary information to enable oral health professionals to assess the effectiveness
The proceedings of the workshop were of their prevention strategies and treatment regimens; help set priorities for thera‐
peutic actions/programs by health care providers; and undertake surveillance.
the Journal of Periodontology and Journal of
Clinical Periodontology. Findings: Based on available methods to assess gingival inflammation, GC could be
simply, objectively and accurately identified and graded using bleeding on probing
score (BOP%)
Conclusions: A patient with intact periodontium would be diagnosed as a GC according
to a BOP score ≥ 10%, further classified as localized (BOP score ≥ 10% and ≤30%) or
generalized (BOP score > 30%). The proposed classification may also apply to patients
with a reduced periodontium, where a GC would characterize a patient with attach‐
ment loss and BOP score ≥ 10%, but without BOP in any site probing ≥4 mm in depth.
KEYWORDS
gingival diseases, gingival hemorrhage, gingivitis
I NTRO D U C TI O N Gingivitis is generally regarded as a site‐specific inflammatory

condition initiated by dental biofilm accumulation2‒4 and character‐
In this review, the term “gingivitis” applies to plaque‐induced gingi‐ ized by gingival redness and edema5 and the absence of periodon‐
vitis alone, rather than non‐dental‐biofilm induced forms of gingi‐ tal attachment loss.6 Gingivitis is commonly painless, rarely leads to
vitis, which carry the relevant prefix, such as “necrotizing”, “plasma spontaneous bleeding, and is often characterized by subtle clinical
cell”, “viral”, “fungal” or “bacterial” gingivitis. These conditions are changes, resulting in most patients being unaware of the disease or
reviewed by Holmstrup et al. 1 unable to recognize it.7
S44 | wileyonlinelibrary.com/journal/jcpe
J Clin Periodontol. 2018;45(Suppl 20):S44–S67.
TROMBELLI et al. | S45
When compared to periodontitis, a peculiarity of plaque‐induced including gingivitis, are based on the use of CPITN.31,32 However,
gingivitis is the complete reversibility of the tissue alterations once the CPITN is not a suitable tool for defining GC.33 It is designed to
the dental biofilm is removed. Notwithstanding the reversibility of screen for the presence of periodontitis, and consequently none of
the gingivitis‐elicited tissue changes, gingivitis holds particular clini‐ the clinical parameters included in the scoring system (i.e., bleed‐
cal significance because it is considered the precursor of periodonti‐ ing, supra‐ or sub‐gingival calculus, pockets) are unique to gingivitis.
tis, a disease characterized by gingival inflammation combined with When using more specific indices to assess gingival inflammation,
connective tissue attachment and bone loss. The evidence support‐ wide variations of gingivitis prevalence are recorded in relation to
ing the relationship between gingivitis and periodontitis stems from varying cut‐off values. In general, the more extended and severe the
longitudinal studies, where development and progression of attach‐ manifestations of the disease that are considered, the less prevalent
ment loss was associated with greater baseline levels of gingival the gingivitis. In children aged 10 to 17 years, gingivitis prevalence
inflammation.8‒13 In contrast, sites with no or minimal progression was very high (91%) when calculated as the proportion of individuals
of attachment loss over time were characterized by the consistent with GI > 0, while it was very low (0.4%) when including only those
absence of gingival inflammation over time.12,14‒18 Overall, these with a mean GI > 1. 23 These observations reinforce the need to
observations suggest that effective long‐term control of gingivitis identify and grade a GC on specific, straightforward, and pragmatic
could prevent progressive attachment loss.13 clinical parameters that combine severity and extent thresholds to
The established relationship between gingival inflammation and assess gingival inflammation on a dentition‐wide basis.
periodontitis calls for the need to establish the clinical criteria that
define a gingivitis case (GC).
Purpose of the review
The purpose of the present review is to summarize the evidence
From gingival inflammation to gingivitis
on clinical, biochemical, microbiologic, genetic markers as well as
case definition
symptoms associated with plaque‐induced gingivitis and to propose
It is clear that defining and grading a gingival inflammatory condi‐ a set of criteria to define a plaque‐induced GC. Such a classification
tion at the site level (i.e. a “gingivitis site”)6 is completely different should: (1) Include the necessary information on disease severity/ex‐
from defining and grading a GC (i.e. a patient affected by gingivitis), tent for oral health professionals to assess the effectiveness of their
and that one “gingivitis site” does not necessarily equate to a GC. preventive measures and treatment regimens; (2) Help set priorities
In fact, when shifting from the description of a “gingivitis site” to for therapeutic actions/programs, with particular emphasis on their
the identification of a GC, the classification process is complicated prognostic relevance (prevention of periodontitis) and impact on
by the absence of clear‐cut criteria that allow for discriminating a quality of life; and (3) Allow the undertaking of surveillance studies
patient with a certain extent/severity of inflamed gingival sites from to monitor the prevalence and distribution of gingivitis consistently
a periodontally healthy patient. In this respect, while clinical gingival within a cohort as well as among different populations.34
inflammation is a well‐defined site‐specific condition for which sev‐ Collectively, the following facts underscore the paramount clini‐
eral measurement systems have been proposed and validated, the cal relevance of the need for GC classification: gingival inflammation
concept of a GC is intended as the means to define the disease at is a ubiquitous and endemic finding in children and adults worldwide;
a patient‐level. Such a definition, i.e., the selection of appropriate, destruction of the periodontal attachment apparatus is associated
distinct, and valid criteria for a GC, becomes more challenging when with only a select number of inflamed gingival sites; gingivitis is
applied to a patient who has experienced attachment loss in the past generally neither painful nor functionally destructive; and gingival
and has been successfully treated. inflammation (as opposed to gingivitis) may not be a disease but a
Although epidemiologic studies indicate consistently that gin‐ variant of health.6 Moreover, when defining the healthy condition in
gival inflammation is a highly prevalent condition, there is hetero‐ a periodontium with normal support, a distinction between “pristine
geneity in the reported prevalence of gingivitis (Table 1).19‒30 Even periodontal health”, defined as a total absence of clinical inflamma‐
though part of this heterogeneity can be interpreted in the light of tion, and “clinical periodontal health”, characterized by an absence or
real, genuine differences in disease occurrence among studied pop‐ minimal levels of clinical inflammation, has been suggested. Overall,
ulations, it is evident that differences among cohorts may well be these considerations seem to imply that a certain amount (extent/
related to variations in the diagnostic criteria used to define a GC. severity) of gingival inflammation of the dentition is compatible with
Epidemiological studies have based the GC definition on epidemi‐ a patient defined as periodontally healthy.35
19‒30
ological indices (Table 1) such as: the Community Periodontal
Index of Treatment Need (CPITN/CPI); average severity of gingival
inflammation (as assessed using gingival indices or bleeding scores); M ATE R I A L S A N D M E TH O DS
average extent of gingival inflammation (assessed as the prevalence
of sites with a certain gingival index or bleeding score); combina‐ Although specific criteria have been introduced in some epidemi‐
tions of severity and extent measures. The majority of epidemio‐ ologic surveys to describe gingival inflammation in large cohorts
logic studies investigating the prevalence of periodontal diseases, (Table 1), no definition for a GC has been universally accepted.
TA B L E 1 Prevalence of gingivitis as derived from national, large‐scale epidemiological studies or reviews
S46
|
Clinical indices to Criteria used to identify a gingivitis

Country Study Population Sample size assess gingivitis case Gingivitis prevalence
United States of America Albandar and Individuals aged 30 to 90, 9,689 BOP Individuals with 6 or more teeth 32.3% (limited: 21.8%;
Kingman 199919 representing approxi‐ present were classified according extensive: 10.5%)
mately 105.8 million to the following criteria:
civilian, non‐institution‐ ‐Extensive gingivitis: 5 or more teeth
alized Americans (or 50% or more of the teeth
examined) with gingival bleeding;
‐Limited gingivitis: 2 to 4 teeth (or
25% to 50% of the teeth
examined) with gingival bleeding.
Individuals who did not fulfill these
criteria were regarded as not
having an appreciable level of
gingival inflammation.
United States of America Li et al. 201020 Subjects recruited by 1,000 GI Mean full‐mouth GI GI < 0.5%: 6.1% of subjects
placing advertisements GI > 0.5: 93.9% of subjects
in local publications GI≥1: 55.7% of subjects
United Kingdom Murray et al. 5 to 15‐year old 69,318 Not reported in Not reported in the review (reported About 50% of subjects had
201521 individuals the review only in surveys included in the gum inflammation
(reported only in review)
surveys included
in the review)
Greece Mamai‐Homata 35 to 44‐year old 1,182 CPI Highest CPI score = 1 (gingival 16.2%
et al. 201022 individuals bleeding)
Romania Funieru et al. 10 to 17‐year old 1,595 GI Prevalence of gingivitis: proportion Gingivitis prevalence: 91%
201723 individuals of any GI mean score > 0
Extent of gingivitis: site prevalence
– proportion of gingival surfaces
affected by gingivitis
Prevalence of gingival bleeding:
proportion of any gingival bleeding
[score 2 and 3 of the GI] present in
at least one gingival surface
Sweden Norderyd et al. Randomly selected 1,010 GI GI = 2 or 3 Mean % of sites with
201524 individuals in each of the gingivitis ranged between
age group of 3, 5, 10, 15, 1.8% to 19.5% depending on
20, 30, 40, 50, 60, 70 age cohort
and 80 years
Hungary Hermann et al. Dentate or partially 4,153 CPI Highest CPI score = 1 (gingival 8%
200925 edentulous adults bleeding)
China Zhang et al. 201026 Adults with ≥ 20 teeth 1,143 GI Mean GI GI≥ 1: 82.2%
(Continues)
TROMBELLI et al.
Murakami and Mariotti6 suggested that the extent, or the number

of gingival sites exhibiting inflammation, can be described as either
0 to 52% (depending on the

2.7%‐27.2% (depending on
localized (<30% of sites are affected) or generalized (≥30% of sites
Gingivitis prevalence
are affected). They also proposed the term incipient gingivitis where,
by definition, only a few sites are affected by mild inflammation, ex‐
Country/study)
pressed as mild redness rather than edema or bleeding on probing
age cohort)
(BOP). However, no clear definition of the most suitable parameter
19.7%
used to characterize the gingival inflammation on a patient‐level is

4.3%
provided. To tackle GC identification and grading, the different pa‐

rameters and methods that are currently available to define or char‐
Criteria used to identify a gingivitis
acterize the gingival inflammation have been thoroughly reviewed.

Highest CPI score = 1 (gingival
Highest CPI score = 1 (gingival
Clinical and biological parameters used to define

gingival inflammation
Clinical parameters
Mean GI≥ 2
bleeding)
bleeding)
Clinical methods to assess the presence and severity of plaque‐in‐

CPI = 1
case
duced gingival inflammation at the site level are based on the evalua‐
tion of crude macroscopic changes occurring in the marginal gingival
tissues during the healthy‐inflamed transition.35 The volume of the
Clinical indices to
assess gingivitis
gingival crevicular fluid (GCF) has been largely adopted in clinical

trials to assess the severity of gingival inflammation at site level.
However, the most commonly used clinical measures for gingival
CPI
CPI
CPI
inflammation mainly consist of qualitative or semi‐quantitative in‐

GI
BOP: bleeding on probing; CPI: Community Periodontal Index; GBI: gingival bleeding index; GI: gingival index.
dices based on visual assessment of gingival characteristics (edema/

each study
Reported in
Sample size
for review
swelling, redness, etc.) and/or the evaluation of the tendency of the

included
22,366
marginal gingiva to bleed upon mechanical stimulation exerted typi‐

2,279
4,967
cally by a periodontal probe. These methods were first described

more than 45 years ago and have not changed much since then
Individuals aged 15 years
Individuals aged 15 years
(Table 2).4,36‒48
7‐8 and 12–13 year‐old
In an attempt to circumvent the subjectivity of examiner scor‐

15 to 44‐year old
ing, non‐invasive methods based on digital technologies were intro‐

duced more recently. These methods mainly aim at measuring the
individuals
individuals
Population
or more
or more
volumetric or color changes that occur in the gingival tissues due to

plaque‐induced inflammation.49‒56 Although their application would
be highly desirable in the diagnosis of gingivitis, no histologic valida‐
tion of these instruments is currently available. Moreover, few stud‐
Australian Research
Kundu et al. 201127
De Muniz 198529
Scheutz 200230
Population Oral
ies have evaluated their reliability in subjects with gingivitis.49,54,56

Health 200928
While some studies reported a positive association between the

Baelum and
Center for
gingival volume and GI changes (without reporting the statistical

Study
strength of the association),49 other studies failed to find a signifi‐

cant correlation between colorimetric assessments and variations in
GI.56 Moreover, additional aspects, including need for standardized
Seychelles, Sierra Leone, Somalia,
Verde, Djibouti, Egypt, Ethiopia,
Algeria, Benin, Burkina Faso, Cap
conditions for their use, restriction of colorimetric assessments to

South Africa, Sudan, Tanzania,
Ghana, Kenya, Lesotho, Libya,
Malawi, Mauritius, Morocco,
the buccal attached gingiva of anterior teeth and need for specific
Namibia, Niger, Nigeria,
(Continued)
adjustments for colorimetric evaluations of pigmented gingival tis‐

sues in specific ethnic groups, limit the potential to apply these tech‐
Zaire, Zimbabwe
nologies reliably or pragmatically to define a GC.

Therefore, for the purpose of this review, the authors limited the
Argentina
TA B L E 1
Australia
analysis of the available clinical parameters as potential candidates

Country
to define a GC to GCF volume, gingival index (GI),37 and gingival

India
bleeding indices.
S48 | TROMBELLI et al.
TA B L E 2 Gingival indices. Re‐adapted from: Bessa Rebelo MA, Corrêa de Queiroz A. Gingival Indices: State of Art. In: Gingival Diseases – Their
Aetiology, Prevention and Treatment, 2011 pp: 41–54. Edited by Dr. Fotinos Panagakos
Index name (authors and Time delay

year) Instrument Sites for assessment (seconds) Graded response
PMA Index (Schour and Visual assessment Each gingival unit is scored. Not stated P (papillary)
Massler 194736) Only the labial surfaces are 0 = normal; no inflammation;
examined. 1 = mild papillary engorgement; slight
increase in size;
2 = obvious increase in size of gingival papilla;
hemorrhage on pressure;
3 = excessive increase in size with spontane‐
ous hemorrhage;
4 = necrotic papilla;
5 = atrophy and loss of papilla (through
inflammation).
M (marginal)
0 = normal; no infiammation visible;
1 = engorgement; slight increase in size; no
bleeding;
2 = obvious engorgement; bleeding upon
pressure;
3 = swollen collar; spontaneous hemorrhage;
beginning infiltration into attached
gingivae;
4 = necrotic gingivitis;
5 = recession of the free marginal gingiva
below the CEJ due to inflammatory
changes.
A (attached)
0 = normal; pale rose; stippled;
1 = slight engorgement with loss of stippling;
change in color may or may not be
present.;
2 = obvious engorgement of attached
gingivae
with marked increase in redness. Pocket
formation present;
3 = advanced periodontitis. Deep pockets
evident.
Gingival Index (Löe and Probe It scores the marginal and Not stated 0 = Normal gingiva;
Silness, 196337) interproximal tissues (four 1 = Mild inflammation – slight change in color
areas for each tooth). The and slight edema but no bleeding on
bleeding is assessed by probing;
probing gently along the wall 2 = Moderate inflammation – redness, edema
of soft tissue of the gingival and glazing, bleeding on probing;
sulcus. 3 = Severe inflammation – marked redness
and edema, ulceration with tendency to
spontaneous bleeding.
Sulcus Bleeding Index Probe Four gingival units are scored Not stated Score 0 – health looking papillary and
(Mühlemann and Son systematically for each tooth: marginal gingiva no bleeding on probing;
197138) the labial and lingual marginal Score 1 – healthy looking gingiva, bleeding on
gingival (M units) and the probing;
mesial and distal papillary Score 2 – bleeding on probing, change in
gingival (P units). color, no edema;
Score 3 – bleeding on probing, change in
color, slight edema;
Score 4 – bleeding on probing, change in
color, obvious edema;
Score 5 – spontaneous bleeding, change in
color, marked edema.
(Continues)
TA B L E 2 (Continued)

Gingival Bleeding Index Unwaxed dental The mouth is divided into six Not stated; Bleeding is recorded as present or absent.
(Carter and Barnes floss segments and flossed in the 30 s is
197439) following order; upper right, allowed
upper anterior, upper left, for
lower left, lower anterior and reinspec‐
lower right. tion
Gingival Bleeding Index Probe Gentle probing of the orifice of 10 If bleeding occurs within 10 seconds a
(Ainamo and Bay the gingival crevice. positive finding is recorded
197540)
Papillary Bleeding Index Probe A periodontal probe is inserted Not stated Score 0 – no bleeding;
(Mühlemann 197741) into the gingival sulcus at the Score 1 – A single discreet bleeding point;
base of the papilla on the Score 2 – Several isolated bleeding points or a
mesial aspect, and then moved single line of blood appears;
coronally to the papilla tip. Score 3 – The interdental triangle fills with
This is repeated on the distal blood shortly after probing;
aspect of the papilla. Score 4 – Profuse bleeding occurs after
probing; blood flows immediately into the
marginal sulcus.
Papillary Bleeding Score Wooden This is performed using a Not stated 0 = healthy gingiva, no bleeding upon
(Loesche 197942) interdental Stim‐U‐Dent®, which is insertion of Stim‐U‐Dent® interproximally;
cleaner inserted interproximally. The 1 = edematous, reddened gingiva, no bleeding
PBS is determined on all upon insertion of Stim‐U‐Dent®
papillae anterior to the second interproximally;
molars. 2 = bleeding, without flow, upon insertion of
Stim‐U‐Dent ® interproximally;
3 = bleeding, with flow, along gingival margin
upon insertion of Stim‐U‐Dent®
interproximally;
4 = copious bleeding upon insertion of
Stim‐U‐Dent ® interproximally;
5 = severe inflammation, marked redness and
edema, tendency to spontaneous bleeding.
Modified Papillary Probe modified the PBI index 0‐30 0 = no bleeding within 30 s of probing;
Bleeding Index (Barnett (Muhlemann, 1977) by 1 = bleeding between 3 and 30 s of probing;
et al. 1980 43) stipulating that the periodon‐ 2 = bleeding within 2 s of probing;
tal probe should be gently 3 = bleeding immediately upon probe
placed in the gingival sulcus at placement.
the mesial line angle of the
tooth surface to be examined
and carefully swept forward
into the mesial papilla. The
mesial papillae of all teeth
present from the second molar
to the lateral incisor were
assessed.
Bleeding Time Index Probe Inserting a Michigan “0″ probe 0‐15 0 = no bleeding within 15 seconds of second
(Nowicki et al. 198144) in the sulcus until slight probing (i.e. 30 seconds total time);
resistance was felt and then 1 = bleeding within 6 to 15 seconds of second
the gingiva was stroked back probing;
and forth once over an area of 2 = bleeding within 11 to 15 of seconds of
approximately 2 mm. first probing or 5 seconds after second
probing;
3 = bleeding within 10 seconds after initial
probing
4 = spontaneous bleeding.
(Continues)

Eastman Interdental Wooden A wooden interdental cleaner is 0‐15 Bleeding within 15 s is recorded as present or
Bleeding Index (Caton interdental inserted between the teeth absent.
cleaner from the facial aspect,
and Polson 198545)
depressing the interdental
tissues 1 to 2 mm. This is
repeated four times
Quantitative Gingival Toothbrush Takes into consideration the Not stated 0 – no bleeding on brushing; bristles free
Bleeding Index (Garg magnitude of blood stains from blood stains;
and Kapoor 198546) covering tooth brush bristles 1 – slight bleeding on brushing; bristle tips
on brushing and squeezing stained with blood;
gingival tissue units in a 2 – moderate bleeding on brushing; about half
sextant of bristle length from tip downwards
stained with blood;
3 – Severe bleeding on brushing; entire bristle
length of all bristles including brush head
covered with blood.
Modified Gingival Index No instrument Same as Gingival Index Not 0 = absence of inflammation;
(Lobene et al. 1986 47) (visual applicable 1 = mild inflammation or with slight changes
assessment) in color and texture but not in all portions
of gingival marginal or papillary;
2 = mild inflammation, such as the preceding
criteria, in all portions of gingival marginal
or papillary;
3 = moderate, bright surface inflammation,
erythema, edema and/or hypertrophy of
gingival marginal or papillary;
4 = severe inflammation: erythema, edema
and/or marginal gingival hypertrophy of
the unit or spontaneous bleeding, papillary,
congestion or ulceration.
Modified Gingival Index No instrument Same as gingival index, but Not 0 = Normal gingiva;
(Trombelli et al. 2004 4) (visual without the bleeding on applicable 1 = Mild inflammation – slight change in color
assessment) probing component. and slight edema;
2 = Moderate inflammation – redness, edema
and glazing;
3 = Severe inflammation – marked redness
and edema, ulceration with tendency to
spontaneous bleeding.
Bleeding on Interdental Interdental brush Inserting a light interdental 30 Bleeding is scored as either present or absent
Brushing Index (Hofer brush placed buccally, just
et al. 201148) under the contact point and
guided between the teeth
with a jiggling motion, without
force. Bleeding is scored for
each interdental site.
Volume of gingival crevicular fluid and the inflammatory infiltrate density.57 Experimental gingivitis
Previous studies demonstrated that the quantification of GCF studies demonstrated a clear association between GCF volume and
volume is a reliable and accurate indicator of gingival inflamma‐ other clinical parameters of gingival inflammation,4 as well as the
tion. 4,57,58
In 60 gingival samples retrieved from buccal sites, GCF concentration of pro‐inflammatory biomarkers.58 Overall, these and
volume increased with increasing site‐specific GI. The GCF volume other studies clearly indicate that GCF volume represents a reliable
reflected GI values, with an evident difference between bleeding quantitative method to assess the severity of site‐specific, plaque‐
sites with moderate inflammation (GI = 2) compared to non‐bleed‐ induced gingival inflammation in the research setting. However, in
ing sites (GI < 2), and paralleled two objective measures of tissue clinical practice, measurement of GCF has proven to be challenging,
inflammation, i.e., the percentage of inflamed connective tissue area costly and time consuming.59 Consequently, GCF volume seems to
be unsuitable to use for a GC definition that fulfills the aforemen‐ following years, based on evidence that during the development of
tioned pragmatic criteria. gingivitis the appearance of bleeding on probing typically precedes
other clinically detectable signs, such as color (redness) or volume
Gingival index changes (edema).38,65 Indeed, apart from a sparse number of studies
37
The GI is based on the combination of visual assessment and me‐ that failed to show significant differences at the histological level
chanical stimulation of the marginal periodontal tissues by prob‐ between bleeding and non‐bleeding gingiva,66,67 the great majority
ing gently along the soft tissue wall of the gingival sulcus/pocket. of studies found that gingival bleeding is an early and accurate sign
Technically, to stimulate the gingival tissues the probe engages of gingival inflammation; some studies reported that sites with gingi‐
approximately 1 to 2 mm of the gingival margin with the probe at val bleeding are histopathologically characterized by a larger and/or
a 45‐degree angle with moderate axial pressure. GI scores are as‐ denser inflammatory connective tissue infiltrate than non‐bleeding
signed on a 4‐point ordinal scale: 0 = absence of inflammation; sites while others reported a significant reduction in inflamed con‐
1 = mild inflammation – slight change in color and little change in nective tissue with the suspension of bleeding.60,66,68‒73 Available
texture; 2 = moderate inflammation – moderate glazing, redness, human histology studies have validated both BOP40 and the bleed‐
edema and hypertrophy; bleeding on pressure; 3 = severe inflamma‐ ing component of GI (i.e., scores 2 and 3)37 as measures of gingival
tion – marked redness and hypertrophy, ulceration with tendency to inflammation. In these studies, gingival biopsies were obtained at
spontaneous bleeding. The validation of the GI comes from histo‐ buccal gingival sites with shallow probing depth in subjects under‐
logical studies in humans where GI scores were significantly corre‐ going a 21‐day experimental gingivitis trial60 or periodontal surgery
lated with histological parameters of inflammation during gingivitis for interproximal pocket elimination.68,74 The results showed an as‐
60
development; specifically, the infiltrated connective tissue volume sociation between BOP and quantitative/qualitative alterations of
and its ratio with the volume of non‐infiltrated connective tissue the inflammatory infiltrate within the connective tissue, with the
increased with increasing GI. Also, a higher percentage of lympho‐ percentage of inflamed connective tissue being significantly greater
cytes and lower percentage of fibroblasts was associated with high at BOP‐positive sites compared to BOP‐negative sites (28.7% vs.
GI scores.60 Since its introduction, the GI has been widely used in 19.1%, respectively).68 Similarly, the ratio between the volume den‐
4,47
clinical periodontal research and, together with its modifications, sities of infiltrated and non‐infiltrated connective tissue was found
it currently represents the most widely used index of gingival inflam‐ to be higher at sites bleeding upon probe stimulation (i.e., having
mation in clinical trials on preventive/therapeutic strategies. a GI = 2) compared to non‐bleeding sites (GI = 0 or 1). Also, a sig‐
To evaluate the GI at the patient‐level,37 a GI score has to be nificant increase in the percentage of lymphocytes and a significant
assigned to four areas (buccal, lingual, mesial and distal) for each of decrease in the percentage of fibroblasts were found for GI = 2 com‐
six index teeth (maxillary right first molar and lateral incisor; maxil‐ pared to GI = 0.60
lary left first premolar; mandibular left first molar and lateral incisor; Gingival bleeding presents additional characteristics in favor of
mandibular right first premolar – the so‐called “Ramfjord teeth”), its application in clinical practice: 1) It is an obvious, objective clinical
and scores of the areas can be averaged to give the GI for the pa‐ sign that may be easily assessed and recorded;39,68,75‒79 2) At a site
tient. The routine application of the GI in clinical practice to define a level, it has been correlated with the severity of the inflammatory
GC, however, presents potential drawbacks: 1)The GI was originally condition of the gingival tissues;60,68 3) With suitable training, it is
proposed to describe gingivitis in pregnant women rather than the possible for general dental practitioners to achieve and maintain high
general population, and the GI scale seems to reflect the specific levels of inter‐examiner consistency in assessing bleeding;80 4) It has
gingival conditions of such individuals. For example, a score of 3 rep‐ prognostic relevance for periodontal deterioration at the site level,
resents a tendency for spontaneous bleeding, which is a rare occur‐ when persistently present during multiple observation intervals. In
rence in the general gingivitis population in contrast to women with this respect, it has been demonstrated that BOP sites (GI = 2) have
pregnancy gingivitis;6 2) Since it is based on both visual inspection higher odds for attachment loss and exhibit greater prevalence of
and mechanical stimulation of the gingival margin, the assessment of progressive severe attachment loss when compared to non‐bleeding
GI will result in a time‐consuming procedure when incorporated in sites (GI = 0 or 1);12 and 5) Patient‐level (i.e., representative of the en‐
a comprehensive, whole‐mouth examination (i.e., 4–6 sites per each tire dentition) data on gingival bleeding can be easily derived from the
tooth present) to obtain data representative of the inflammatory site‐specific measurements, e.g., frequency or proportion of bleeding
burden of the entire dentition; and 3) Intra‐ and inter‐examiner reli‐ sites, thus generating parameters that can be effectively used to in‐
ability and reproducibility of the GI, particularly the component as‐ form and motivate the patient41,70,71,81 as well as monitor the efficacy
sociated with visual inspection, while reported as very good in some of preventive and treatment strategies of periodontal diseases.82‒84
61
studies, appears problematic even after calibration and training
sessions in other reports.62,63 Methods to assess gingival bleeding: gingival stimulation
Varying methods have been proposed to assess gingival bleeding.
Gingival bleeding Among those, the most commonly used are: BOP score,40 scores
Gingival bleeding was first incorporated in a clinical periodontal of 2 to 3 of the gingival index37 and the angulated bleeding index
64
index in 1958. Much interest was given to this clinical sign in the (AngBS).4,85‒87 These methods are based on a different diagnostic
maneuver with respect to probing stimulation of the gingival tissues. screening system in both clinical and epidemiological practice; and
While the probe is inserted to the bottom of the gingival sulcus/ 4) The BOP score is the bleeding index that has most often been
pocket with a standardized force when assessing BOP, it is used to correlated with patient‐related periodontal prognosis, self‐reported
exert a gentle pressure on the gingival margin with a specific an‐ symptoms91 and quality of life.35,92‒94
gulation when assessing GI or AngBS. Under conditions of natu‐
rally occurring gingivitis, a significant intra‐subject correlation was Methods to assess gingival bleeding: dichotomic or graded
observed between BOP and bleeding of the marginal gingiva (i.e., assessment
GI 2 and 3).88,89 Concordance between BOP and GI bleeding was Given that the clinical assessment of gingival inflammation at a site‐
found to be dependent on the probing depth (PD) of examined sites. specific level is based on BOP, the extent of gingival inflammation in
While 85.4% of agreement was found for the detection of bleed‐ a dentition is related to the proportion of BOP+ sites. However, BOP
ing at sites with PD > 4 mm, 77.7% of agreement was observed be‐ may also be used to provide the severity of the inflammatory con‐
tween absence of GI bleeding (i.e., GI ≤ 1) and absence of BOP at dition of the gingival tissues, as expressed by qualifying the bleed‐
shallow (≤2 mm) pockets.88 Despite their correlation, however, GI ing tendency42,46,95 or its timing after probe insertion.41,44 Although
bleeding and BOP seem not to have the same potential to detect useful for research purposes, it appears that the use of quantifica‐
gingival inflammation and, therefore, should not be considered as tion indices to routinely qualify BOP at a site level may be time con‐
equivalent parameters. In this respect, some studies reported a ten‐ suming, with variations in the grading scale difficult to detect during
dency towards higher bleeding prevalence for GI assessment com‐ a routine comprehensive periodontal examination.96
pared to BOP,88 while others reported a consistently higher (about
10%) proportion of bleeding sites when probing at the bottom of Methods to assess gingival bleeding: probe/probing
the sulcus/pocket.89 On the basis of the finding that in young sys‐ characteristics
temically healthy dental students the number of GI bleeding sites The periodontal clinical signs detected through probing include
was similar to the number of BOP+ sites after a period of supervised bleeding tendency, PD, and clinical attachment level (CAL). Early
oral hygiene, while it was double after a 21‐day period of experi‐ on, it became evident that assessments of PD and CAL are subject
mentally‐induced plaque accumulation, it has been suggested that to significant variability.97 In fact, a large body of literature is dedi‐
bleeding upon stimulation of the marginal gingiva seems to be a bet‐ cated to the technical and clinical aspects of periodontal probing
ter indicator of early inflammatory changes in the gingival tissues as it relates to PD and CAL assessments.98‒104 The development
87
when compared to BOP to the bottom of the pocket. In contrast, of pressure‐sensitive, controlled‐force, automated, and computer
a large scale study has confirmed that outcomes of the two stimula‐ controlled probes105‒113 was the result of the strong interest in de‐
tion approaches (marginal versus bottom of the pocket) are highly termining the relationship between CAL and histologic attachment
correlated (r = 0.89), with probing the bottom of the pocket resulting level and efforts to minimize the variability associated with prob‐
in 1.5‐fold increase in average prevalence of bleeding‐positive sites ing determinations. Despite providing controlled forces, improved
per patient.90 Therefore, there is no consensus on the best gingival instrument precision, and electronic data capture, electronic probes
bleeding measure to incorporate in a GC definition. do not offer a substantially improved measurement error.100,114 This
Within the context of a GC definition, some practical consider‐ fact, combined with the increased time and cost associated with
ations may point to probing to the bottom of the sulcus/pocket (as the use of electronic probes,115 makes it easy to understand why
performed when assessing BOP) as the preferred method to stim‐ manual probes remain the instrument of choice in clinical practice.
ulate and assess gingival bleeding: 1) The detection and recording There is also evidence that this lack of improved reproducibility with
of bleeding upon stimulation by a probe inserted in the gingival certain electronic probes may be related to patient discomfort, with
sulcus is a part of the comprehensive periodontal examination as the patient being a significant variable when determining probing
included in periodontology education programs; 2) Probing to the reproducibility.116
bottom of the sulcus/pocket may diagnose the presence of gingival Available data showed that probing force is a significant factor
inflammation while simultaneously assessing other relevant clinical in determining BOP response. Probing force has a direct and linear
parameters (attachment level, probing depths), which gingival mar‐ effect on BOP prevalence, with forces greater than 0.25 N (25 g)
gin bleeding cannot achieve. Since a site (and thus, a patient) with increasing the risk of false‐positive readings,117‒119 while use of con‐
gingivitis should not present with attachment loss, a single probing stant force results in greater reproducibility of bleeding scores.120
maneuver allows collection of the information necessary to detect The probing force applied by different clinicians varies significantly
the presence of both gingival inflammation and attachment loss. On and often exceeds the 25‐g threshold.105,121,122 From a patient per‐
the contrary, gingival bleeding assessment using GI does not incor‐ spective, greater probing forces are likely to exceed the pain thresh‐
porate the evaluation of the integrity of the periodontal support and, old in healthy sites123 and even more likely in inflamed sites.124
therefore, cannot be considered exhaustive when aiming to defini‐ Another technique‐related factor is angulation/placement of the
tively establish a GC diagnosis, i.e., when needing to differentiate probe, which was reviewed in the previous section.
between gingivitis and periodontitis; 3) Bleeding following probing In terms of instrument characteristics, probes with different tip
to the sulcus/pocket base is performed as part of the CPITN/CPI diameters exhibit varying abilities to penetrate gingival tissues.125,126
This is consistent with the observation that thinner probes may elicit the evaluation of the prevalence, severity and extent of gingival
127
more pain during periodontal examination. Although there is no inflammation has been evaluated in a few studies,133‒137 there is
consensus regarding optimal probe tip diameter specifically for BOP limited information on which partial mouth protocol shows the
determination, limited evidence suggests that a probe tip diameter best accuracy in representing the severity/extent of gingivitis as
of 0.6 mm provides the best discrimination between diseased and assessed by BOP;137 2) Clinical assessments to identify and grade
healthy sites.126 a GC are necessarily incorporated in a comprehensive, full‐mouth
Research has been conducted on the effect of probe tine shape examination, which also aims at detecting and grading attach‐
(parallel, tapered, tapered ball‐tipped) on PD assessment under dif‐ ment loss. Although a recent systematic review has pointed out
ferent probing forces;128 the results indicate that tine shape also im‐ that some partial‐mouth examination protocols well approximated
pacts upon PD measurements. However, specific information on the a full‐mouth protocol for prevalence, severity, and extent esti‐
impact of probe tine shape on BOP has not been reported. mates of periodontitis,138 their performance when applied to the
In the context of probe characteristics and BOP assessment, it periodontitis case definitions suggested by the CDC/AAP139 or
should be noted that commercially available probes have shown sig‐ the European Federation of Periodontology140 remains unknown.
nificant variation in dimensions (probe tine diameter and calibration Therefore, as of now, the case definition of periodontitis (and, con‐
of markings) when different samples were examined, even from the sequently, of a GC) remains based on the full‐mouth examination
same production batch.129‒131 If millimeter markings are not relevant of 4/6 sites per each tooth present;141 and 3) Albeit a viable, and
for BOP assessment, the probe diameter is. Although the available oftentimes, desirable approach in the research setting, the option
literature suggests that probe diameter variability has declined in to partially assess the dentition of a patient presenting in one's clin‐
more recent years, standardization of the manufacturing parameters ical practice for comprehensive examination is not really an option.
for periodontal probes would help minimize such variability. Consequently, on the basis of the available evidence and the con‐
Although, as mentioned above, clinicians often use a probing siderations reported above, the definition of a GC should be based
force > 25 g,105,121,122 with the average maximum probing force re‐ on the full‐mouth evaluation of all sites available for examination.
ported to be in the 50‐ to 70‐g range,122 such differences in force
magnitude have been shown to result in consistent but moderate
Biomarkers in oral fluids
changes in BOP prevalence. For example, the mean BOP response
when a 25‐ and a 50‐g probing force were applied varied by 3 to 16 With increasing knowledge of gingivitis pathophysiology, specific bio‐
percentage points, depending on patient status (pre‐ or post‐treat‐ markers detected in oral fluids have emerged as potential candidates
ment, high or low BOP tendency) and study.117‒119 The lack of infor‐ to help characterize and thus define a GC. Among the most promising
mation in the literature on the prevalence of patients who fall within biomarkers are inflammatory cytokines, indicators of the inflamma‐
a particular mean BOP range given a specific probing force applied, tory host response, which can be recovered from GCF and saliva.142,143
combined with the fact that the aforementioned studies were based
on a limited number of participants (10 to 12), makes it difficult to GCF proteomics
fully ascertain the true impact of the probing force on the catego‐ Although several studies have investigated GCF proteomics under
rization of patients based on their BOP response. Nevertheless, conditions of gingival inflammation, most of them concentrated on
further review of the data reported from patients with optimal oral the healthy‐inflamed transition at specific sites. Proteomic analyses
hygiene118,119 suggests that use of a 25‐g force results in a majority conducted on GCF obtained from healthy sites (i.e., sites with GI = 0,
(∼70%) of these patients having a BOP response of ≤10%. PD ≤ 3 mm, attachment loss ≤1.5 mm) of periodontally healthy sub‐
jects showed that GCF proteomics is rather complex, consisting of
Methods to assess gingival bleeding: full‐mouth vs. partial‐ approximately 200 distinct proteins, 57% of which were identified
mouth assessment also in plasma and 43% were apparently not plasma related.144 This
Although a comprehensive periodontal examination is generally clearly indicates that even though serum contributes to GCF com‐
based on the examination of all teeth at mesio‐buccal, mid‐buccal, position, GCF is an oral fluid with a distinctive proteomic profile.
disto‐buccal, mesio‐lingual, mid‐lingual, disto‐lingual (MB‐B‐DB‐ Moreover, this quantitative analysis of GCF showed that the domi‐
ML‐L‐DL) surfaces,132 a partial mouth examination protocol (based nant proteins in conditions of periodontal health were intracellular
on a minimum number of selected quadrants, teeth and sites repre‐ and nucleotide proteins (25%) and hydrolytic enzymes (19%).144
sentative of the entire dentition) would be highly desirable for both Under experimental gingivitis conditions, the GCF proteomic pro‐
patients and oral health professionals. file of inflamed sites showed substantial changes when compared to
At present, however, the everyday clinical application of a par‐ that observed in periodontal health. In particular, only 28 proteins
tial‐mouth examination protocol in defining the extent of gingival out of 186 identified at inflamed sites were found to be common
inflammation remains limited by the following issues: 1) Available with those detected at healthy sites.145
validation data are not sufficient to identify the most accurate par‐ More recently, there has been a further attempt to character‐
tial‐mouth examination protocol. Although the level of agreement ize the GCF profile of a patient with gingivitis (i.e., a patient with a
between partial‐mouth and full‐mouth examination protocols in given amount of gingival inflammation and no attachment/bone loss)
TA B L E 3 Studies comparing GCF biomarker levels in gingivitis and other periodontal conditions (i.e., health and periodontitis)
S54
|
Year of Sites for GCF Periodontal health (H): Gingivitis (G): case Periodontitis (P): case
Authors publication Population assessment case definition definition definition Main results
Ulker 2008 Recruited at the Faculty In the G group, GCF Not reported Not reported – No significant differences in the
et al.146 of Dentistry, University of samples were levels of cystatin C, TNF‐α, and
Gazi, Turkey collected from four IL‐1b between G and H.
(G = 10, H = 25) maxillary upper
incisors that were
affected by gingivitis.
Perozini 2010 Recruited at the Two randomly selected According to AAP 1999 According to AAP 1999 According to AAP 1999 In G, IL‐1b concentration was
et al.147 University of Taubatè, teeth in each patient (systemically healthy (clinical signs of (clinical signs of inflamma‐ significantly lower compared to P
Brazil with no history of inflammation without tion with attachment loss) and similar to H. ALP levels in G
(P = 12, G = 12, H = 12) periodontal disease) attachment loss) were significantly lower than P
and higher than H.
Hardan 2011 Recruited at Temple 4 sites (1 per quadrant) No CAL loss No CAL loss ≥ 4 teeth (≥ 1 tooth in each GCF levels of hydrophobic
et al.148 School University, US The sites were the most < 5 sites with GI = 2 ≥ 5 sites with GI = 2 quadrant) with ≥ 1 site aminoacids showed a significant
(P = 23, G = 18, H = 32) representative of with CAL≥ 4 mm increase from healthy to G
each condition. condition. No difference in GCF
levels of sulfur compounds
between H and G.
Becerik 2012 Recruited at the School of Mesio‐buccal aspects of PD ≤3 mm Varying degrees of Aggressive P: IL‐11 total amount was significantly
et al.149 Dentistry, Ege two anterior teeth No gingival recessions gingival inflammation CAL ≥5 mm and PD≥ 6 mm higher in Chronic P compared to
University, Izmir, attributable to CAL ≤2 mm at ≥90% of on ≥8 teeth, at least 3 of G. No significant differences in
Turkey periodontitis sites those are other than total amounts of IL‐1b, IL‐6,
(Aggressive P = 20, CAL≤ 2 mm at ≥90% of Radiographic distance central incisors or first OSM, and LIF between G and
Chronic P = 20, G = 20, sites between the CEJ and molars either P or H.
H = 20) BOP score < 10% bone crest ≤3 mm Radiographic bone loss G had elevated OSM concentration
Radiographic distance at > 90% of the ≥30% of the root length when compared to H, and
between the CEJ and proximal tooth sites on affected teeth; significantly higher LIF concen‐
bone crest ≤3 mm Chronic P: tration than Aggressive P. No
at > 90% of the CAL ≥5 mm and PD ≥6 mm significant differences in
proximal tooth sites in multiple sites of all four concentration of IL‐1b, IL‐6, and
quadrants of the mouth. IL‐11 between G and either P or
Moderate‐to‐severe H.
alveolar bone loss
present on radiographs
Gokul 2012 Recruited at the Not reported Clinically healthy Clinical signs of Clinical signs of inflamma‐ TNF‐α levels in G were significantly
et al.150 Department of periodontium with inflammation with no tion with attachment loss higher than H, and similar to P.
Periodontics, no evidence of evidence of attach‐ and radiographic bone
Priyadarshini Dental disease ment loss and loss
College & Hospital, (Ramfjord's Periodontal radiographic bone loss (Ramfjord's Periodontal
Chennai, India Disease Index = 0) (Ramfjord's Periodontal Disease Index = 4–6)
(P = 20, G = 20, H = 20) Disease Index = 1–3)
TROMBELLI et al.
(Continues)
Year of Sites for GCF Periodontal health (H): Gingivitis (G): case Periodontitis (P): case
Authors publication Population assessment case definition definition definition Main results
Ertugrul 2013 Recruited at the Faculty 4 sites in 4 Ramfjord No CAL > 2 mm BOoP score > 50% Aggressive P: IN G, CCL28, IL‐8, IL‐1b and TNF‐a
TROMBELLI et al.
et al.151 of Dentistry, Yuzuncu teeth in H and G No PD > 3 mm Radiographic distance 16–30 years of age levels
Yil University, Turkey subjects BOP score < 15% between the CEJ and ≥ 20 natural teeth Were significantly higher compared
(Aggressive P = 21, 4 BOP+ sites in 4 Radiographic distance bone crest < 3 mm ≥ 6 incisors and/or first to H and significantly lower
Chronic P = 21, G = 21, Ramfjord teeth in G between the CEJ and at > 95% of the molars with ≥ 1 site with compared to Chronic P and
H = 21) subjects bone crest < 3 mm proximal tooth sites PD and CAL > 5 mm Aggressive P.
4 BOP+ sites in 4 teeth at > 95% of the ≥ 6 teeth other than first
showing the deepest proximal tooth sites molars and incisors with
pockets in the ≥ 1 site with PD and
chronic and CAL > 5 mm
aggressive P subjects Chronic P:
Inflammation in the gingiva
Vertical and horizontal bone
loss on radiographs
PD≥ 5 mm in ≥ 6 sites of at
≥ 4 single‐rooted teeth
with CAL≥ 4 mm
Kinney 2014 Recruited at the Michigan Mesiobuccal aspect of 8 CAL < 3 mm CAL < 3 mm ≥ 4 sites with CAL > 3 mm GCF biomarkers associated with
et al.152 Center for Oral Health sites. No PD > 4 mm No PD > 4 mm ≥ 4 sites with PD > 4 mm stable and progressing cases were
Research clinic, Ann Site selection was BOP score ≤ 20% BOP score > 20% ≥ 4 sites with radiographic evaluated.
Arbor, Michigan based on group No radiographic No radiographic alveolar bone loss
(P = 44, G = 24, H = 15) classification (in alveolar bone loss bone loss
patients without
periodontitis, sites
with PD less than
4 mm and/or CAL
less than 3 mm were
ranked higher; in
patients with
gingivitis, sites were
ranked even higher if
they had BOP).
Huynh 2015 Patients attending the The sites chosen were PD≤ 3 mm BOP score > 5% ≥ 2 sites with PD≥ 5 mm Forty‐two proteins were considered
et al.153 Royal Dental Hospital of the most representa‐ BOP score≤ 5% mGI≥ 1 BOP score≥ 5% to have changed in abundance. Of
Melbourne and staff at tive of each condition. mGI < 1 PI ≥ 20% mGI≥ 1 note, cystatin B and cystatin S
the Melbourne Dental PI < 20% No radiographic bone PI I≥20% decreased in abundance from H to
School, Australia. loss radiographic bone loss G and further in P. Complement
proteins demonstrated an increase
from H to G followed by a
decrease in P.
|
S55
(Continues)
(Table 3).146‒155 Overall, these studies indicate that the GCF pro‐
ALP: alkaline phosphatase; BOP: bleeding on probing; CAL: clinical attachment level; CCL28: mucosa‐associated epithelial chemokine; CEJ: cementum‐enamel junction; mGI: modified gingival index; IL‐1ß:
interleukin 1ß; IL‐6: interleukin 6; IL‐8: interleukin 8; IL‐11: interleukin 11; IL‐35: interleukin 35; IL‐37: interleukin 37; LIF: leukemia inhibitory factor; OSM: oncostatin M; PD: probing depth; PI: Plaque Index;
between G and either H or P. IL‐37
The IL‐37 total amount was similar
IL‐35 levels in G were significantly
teomic profile of gingivitis subjects is qualitatively and quantitatively
lower in P compared to G and H.

concentration was significantly
lower than H and similar to P.
different from that of periodontal health; more specifically, a greater
number of proteins have been found in gingivitis compared to peri‐
odontal health.153 Moreover, the amount of some proteins (e.g.,
IL‐1b, ALP, complement factors, MMP‐9, fibronectin, lactotrans‐
ferrin precursors, alpha‐actinin) is higher in gingivitis compared to
Main results
periodontal health,147,153 while other proteins (e.g., cystatin‐B, cys‐

tatin‐S) are present in lower amounts in gingivitis.153
Despite these reported GCF proteomic differences between
periodontal health and gingivitis, the overall paucity of data on the
≥ 50% alveolar bone loss in
≥ 50% alveolar bone loss in

PD≥ 5 mm, CAL≥ 4 mm
≥ 4 teeth in each jaw with
≥ 4 teeth in each jaw with GCF proteomic profile of gingivitis subjects, along with the hetero‐
PD ≥ 5 mm and CAL ≥
Periodontitis (P): case
geneity between studies in terms of GC definition (Table 3), site se‐
BOP score > 80% lection for GCF sampling, and GCF sampling methods, as well as the
BOP score > 50%
≥ 2 quadrants
≥ 2 quadrants
practical limitations in performing such an assessment chairside in
daily practice, currently eliminate the possibility to use the GCF pro‐
definition
4 mm
teomic profile as the basis for GC definition.
Salivary proteomics
between the CEJ and
Radiographic distance
Whole mouth saliva (WMS) is not only composed of major and minor
bone crest≤ 2 mm
Gingivitis (G): case
salivary gland secretions but also contains mucosal transudates from

BOP score≥ 20%
BOP score≥ 20%
all surfaces of the mouth, lymphoid tissues, oropharynx, and GCF.

No CAL loss
PD < 4 mm
PD≤ 3 mm
Saliva, a hypotonic aqueous solution that contains proteins, pep‐

definition
tides, enzymes, hormones, sugars, lipids, growth factors and a va‐

riety of other compounds, has a complex composition.156 Proteomic
studies on human saliva revealed > 1,000 proteins and peptides.143
between the CEJ and
Periodontal health (H):
Radiographic distance
Some studies have characterized the salivary proteomic profile

bone crest≤ 2 mm
BOP score < 20%
BOP score < 20%
of gingivitis (i.e., a patient with a given amount of gingival inflamma‐

case definition
tion and no attachment/bone loss) compared to periodontal health

No CAL loss
PD≤ 3 mm
(Table 4).146,154,155,157‒160 The analyses showed that gingivitis was

PD < mm
associated with significantly increased amounts of blood proteins

(serum albumin and hemoglobin), immunoglobulin peptides and ker‐
atins,158 PGE2 and MIP‐1α,160 and more than double the amounts of
GI≥ 2 and PD≤ 3 mm;
GI≤ 1 and PD≤ 3 mm;
GI≥ 2 and PD≥ 5 mm
selected according to
In G: BOP+ sites with
multirooted tooth.
In P: BOP+ sites with

In H: BOP‐ sites with
the baseline clinical
MMP‐8, MMP‐9, and IL‐6.157 In periodontal health, salivary cystatins

2 non‐adjacent sites
2 sites in 1 single‐
appeared to be more abundant.158 Similarly to GCF proteomics, the

measurements
rooted and 1
Sites for GCF
use of salivary proteomics to identify a patient with gingivitis has

assessment
substantial limitations, mainly due to the heterogeneity in gingivitis

definition among studies (Table 4), as well as the methodology used
for proteomic profiling.
Recruited at the Faculty
(P = 20, G = 20, H = 20)
(P = 20, G = 20, H = 20)

Faculty of Dentistry,
Izmir Katip Cxelebi
of Dentistry, Izmir,
Microbiologic markers
University, Izmir,
Periodontology,
Department of
Recruited at the
From the earliest studies of Löe and coworkers, which established

Population
Turkey
Turkey
the bacterial etiology of gingivitis in the 1960s, 2,3 to investigations

reported in the late 1990s,161‒165 the microbiological assessment
TNF‐α: tumor necrosis factor α.
of gingivitis (and periodontitis) was based on bacterial culture, and

(Continued)
morphological, biochemical and other targeted analyses of col‐

publication
lected plaque samples. These studies identified several Gram‐posi‐

Year of
2015
2015
tive anaerobes (e.g., Actinomyces viscosus, Parvimonas micra (formerly

Micromonas and Peptostreptococcus micros)), Gram‐positive facul‐
TA B L E 3
tative species (Streptococcus spp), and Gram‐negative anaerobes

Köseoğlu
et al.154
et al.155
Authors
Saglam
(e.g., Campylobacter gracilis, Fusobacterium nucleatum, Prevotella

intermedia, Veillonella parvula) as associated with gingivitis,166 with
TA B L E 4 Studies investigating salivary biomarker levels in gingivitis and other periodontal conditions (i.e., health and periodontitis)
Year of Periodontal health (H): Gingivitis (G): Periodontitis (P):

Authors publication Population case definition case definition case definition Main results
146
Ulker et al. 2008 Recruited at Faculty of Dentistry, University Not reported Not reported – No significant differences in cystatin C,
TROMBELLI et al.
of Gazi, Turkey TNF‐α and IL‐1ß levels between G and H

(G = 10, H = 25)
Ramseier 2009 Recruited at the Michigan Center for Oral CAL < 3 mm CAL < 3 mm ≥4 sites with G showed levels of MMP‐8 and MMP‐9 that
et al.157 Health Research clinic, Ann Arbor, PD > 4 mm PD > 4 mm CAL > 3 mm were intermediate between H and P
Michigan, US BoP score ≤20% BoP score > 20% ≥4 sites with
(P = 49, G = 32, H = 18) No radiographic bone loss No radiographic PD > 4 mm
bone loss ≥4 sites with
radiographic bone
loss
Da R. 2011 Recruited at the School of Dentistry, Federal BOP score < 10% No CAL loss – G was associated with increased amounts of
Goncalves University of Espirito Santo, Brazil PD < 3 mm BOP score > 50% serum albumin and hemoglobin, immuno‐
et al.158 (G = 10, C = 10) PD > 3 mm globulin peptides and keratins. Cystatins
in > 50% of were more abundant in H
sites
Kinney 2011 Recruited at the Michigan Center for Oral CAL < 3 mm CAL < 3 mm ≥4 sites with Same cohort as Ramseier et al. 2009157. The
et al.159 Health Research clinic, Ann Arbor, No PD > 4 mm No PD > 4 mm CAL > 3 mm paper focuses on the association of salivary
Michigan, US No radiographic bone loss No radiographic ≥4 sites with biomarkers and periodontal disease
(P = 41, G = 23, H = 15) BOP score ≤20% bone loss PD > 4 mm progression.
BOP score > 20% ≥4 sites with
radiographic bone
loss
Köseoğlu 2015 Recruited at the Department of No CAL loss No CAL loss ≥ 4 teeth in each jaw IL‐35 levels in G were significantly lower
et al.154 Periodontology, Faculty of Dentistry, PD ≤3 mm PD ≤3 mm with PD ≥ 5 mm, than H and significantly higher than P
Izmir Katip Cxelebi University, Izmir, BOP score < 20% BOP score ≥20% CAL ≥ 4 mm
Turkey ≥ 50% alveolar bone
(P = 20, G = 20, H = 20) loss in ≥ 2
quadrants
BOP score > 50%
Saglam 2015 Recruited at the Faculty of Dentistry, Izmir, PD < 4 mm PD < 4 mm ≥ 4 teeth in each jaw Similar levels of IL‐37 between H, G, and P
et al.155 Turkey (G = 20, H = 20) BOP score < 20% BOP score≥20% with PD ≥ 5 mm
Radiographic CEJ‐bone Radiographic and CAL ≥ 4 mm
crest ≤ 2 mm CEJ‐bone BOP > 80%
crest ≤2 mm ≥ 50% alveolar bone
loss in ≥ 2
quadrants
Syndergaard 2014 Recruited at the University of Kentucky No CAL ≥2 mm No CAL≥ 2 mm – Concentrations of MIP‐1α and PGE2 were
et al.160 College of Dentistry, Kentucky, US PD ≤4 mm PD≤ 4 mm significantly
(G = 40, H = 40) BOP score < 20% BOP score≥ 20% Higher (2.8 times) in G compared to H
|
BOP: bleeding on probing; CAL: clinical attachment level; CEJ: cementum‐enamel junction; IL‐1ß: interleukin 1ß; IL‐6: IL‐35: interleukin 35; IL‐37: interleukin 37; MIP‐1α: macrophage inflammatory
protein 1α; MMP‐8: matrix metalloproteinase 8; MMP‐9: matrix metalloproteinase 9; PD: probing depth; PGE2: prostaglandin E2; TNF‐α: tumor necrosis factor α.
S57
the flora becoming more diverse with time and the development inflammation were evaluated for their relationship with CRP levels
167
and progression of gingivitis. Efforts to identify microbiologic in serum. While in some studies CRP levels were found to be signifi‐
differences among persons with a stronger or weaker gingival in‐ cantly positively correlated with papillary bleeding index186 or GI,184
flammatory response to plaque accumulation did not find significant other authors failed to find an association between CRP levels and
differences.161 Although quantitative differences were consistently GI,185 BOP,185,187 or the number of sextants with at least one BOP+
identified for targeted species among sites characterized by gingivi‐ site.188 Certain factors may have contributed to the heterogeneity
162‒164
tis and periodontitis or health, none of the associated bacterial among these findings. First, criteria for GC definition varied greatly
species were unique to gingivitis and, therefore, their presence can‐ among studies. Second, control of potential confounders through
not be considered pathognomonic. adequate statistical analyses (e.g., multivariate models) was applied
The introduction in the late 90s of open‐ended molecular meth‐ only in some studies.187,188 Overall, the above mentioned findings
ods and their application to the detection of microbes broadened seem to demonstrate that the inflammation of marginal gingival tis‐
significantly the spectrum of bacterial species associated with peri‐ sues determines an increase in systemic inflammation, assessed in
odontal diseases, with many previously unidentified and/or unculti‐ terms of CRP levels. However, other studies have failed to demon‐
168‒171
vated bacteria linked with periodontitis. In the last few years, strate potentially relevant systemic effects during gingivitis devel‐
these molecular techniques have been applied, along with novel sta‐ opment.189 Therefore, the relationship between severity of gingival
tistical approaches, to the study of the biofilm associated with gingi‐ inflammation and severity of systemic inflammation in patients with
vitis and compared to health and periodontitis.172‒177 These studies gingivitis remains unclear.
have demonstrated that the transition from health to disease follows
the principles of primary ecological succession, with change in abun‐
Genetic markers
dances of indigenous species, rather than acquisition of newer organ‐
isms. Even as these studies identified previously unrecognized species Two specific pieces of information suggest that susceptibility to
in gingivitis, they confirmed that the biofilms associated with gingivitis gingivitis may be genetically controlled.190,191 The first line of evi‐
and periodontitis share most species (albeit with quantitative differ‐ dence comes from studies of patients with Down syndrome. Despite
ences). Emerging evidence suggests that clusters of bacteria, rather no differences in plaque accumulation rates, patients with Down
than individual species, might be of use as diagnostic markers for each syndrome, compared to age‐ and sex‐matched genetically healthy
disease; and that bacterial functions (e.g., proteolysis, flagellar assem‐ controls, exhibit more extensive gingival inflammation and at much
bly, bacterial motility) may be a more robust discriminant of disease earlier times.192 The second line of evidence comes from studies on
than species. While these early novel findings support a gene‐cen‐ twins. Michalowicz et al.193 studied monozygous and dizygous adult
178‒182
tric rather than a species‐centric approach to disease causation, twin pairs and reported that, based on ratios of within‐pair variances
further studies are required to better characterize such bacterial clus‐ or heritability estimates, there was a significant genetic component
ters and gene functions and to validate their potential use both as a for gingivitis and other clinical parameters. For gingivitis, in particu‐
diagnostic tool and as response to treatment monitoring tool.183 lar, they estimated from reared‐apart monozygous twins that 82%
of the population variance may be attributed to genetic factors.193
These findings provide strong support for the role of genetic make‐
Systemic inflammation markers (CRP)
up in gingivitis susceptibility.
As for other chronic inflammatory diseases, the relationship be‐ Recent evidence is available evaluating whether genetic charac‐
tween periodontal diseases (including gingivitis) and systemic levels teristics, in general, and gene polymorphisms, in particular, may con‐
of inflammatory markers has been evaluated. The biologic mecha‐ tribute to exacerbated gingival inflammation in response to plaque
nisms supporting the plausibility of this association rely on the entry accumulation. Since the host immune response is a dominant gene
of pathogenic bacteria from the biofilm of periodontally diseased expression pathway during the onset and resolution of gingival in‐
sites into the blood stream and on the entry into the circulation of flammation, with several genes being significantly up‐ or downreg‐
excess local levels of host‐derived inflammatory mediators. ulated,194 particular emphasis has been placed upon evaluating the
Among the investigated biomarkers, particular attention has potential association between cytokine gene polymorphisms and
been paid to C‐reactive protein (CRP), which is produced in response gingival inflammation in either observational, cohort studies195‒200
to many forms of trauma or diseases and contributes to host defense or experimental gingivitis trials. 201‒204 Although the available evi‐
as part of the innate immune response. Studies that evaluated the dence suggests a role for some gene polymorphisms in determining
association between gingivitis and serum levels of CRP universally the susceptibility to plaque‐induced gingival inflammation, defini‐
identified gingivitis as a condition characterized by serum CRP lev‐ tive associations between ≥1 genetic indicators and the severity of
els which are intermediate between those measured in periodontal gingival inflammation are not yet available, in part because of the
health and periodontitis, although differences in serum CRP levels limited number of gene loci investigated and the small number of
observed between gingivitis and the other periodontal conditions subjects included in pertinent studies. 205 To date, a limited number
184‒186
did not consistently reach statistical significance in all studies. of studies have attempted to investigate the genetic profile of gin‐
In subjects with gingivitis, the severity and extent of gingival givitis and healthy cases (Table 5).197,200,206‒208 However, large‐scale
TROMBELLI et al.
TA B L E 5 Case‐control studies investigating the association between gene polymorphisms and gingivitis (versus healthy controls)
Year of Periodontal health (H): case Gingivitis (G): case Investigated gene
Authors publication Population definition definition polymorphisms Main results
206
Dashash et al. 2006 248 whites Healthy gingiva Clinical evidence of IL‐10 ‐1082 The GCC/GCC genotype, which has been
Aged 8 to 12 years And no evidence of bleeding gingivitis assessed by IL‐10 ‐819 associated with increased production of IL‐10,
(G = 164, H = 84) on probing or clinical signs gingival and bleeding IL‐10 ‐592 was significantly more frequent in H than in G.
of inflammation on probing indices
Dashash et al.197 2007 146 whites Healthy gingiva and had Presence of IL‐1RN Significant association between IL‐1Ra genotype
Aged 8 to 12 years Neither evidence of bleeding Bleeding on probing at and periodontal status (H vs G). The IL‐1RN*2
(G = 98, H = 48) on probing nor clinical signs any site, as deter‐ allele (A2) was significantly more frequent in H,
of inflammation mined by gingival and and the carriage of A2 seemed to be protective
papillary bleeding on against gingivitis.
probing indices
Holla et al. 207 2008 455 whites GI = 0 Total sum of GI values at IL‐6‐174 Significant differences in haplotype frequencies
Aged 11 to 13 years At all 24 examined sites 24 examined sites≥ 4 IL‐6‐572 between G and H. The CGA haplotype was
(G = 272, H = 183) IL‐6‐597 significantly more frequent in G than in H. The
IL‐6 – 174C allele was more frequent in G than in
H, and allele C remained a risk factor for G
regardless of plaque or gender.
Vokurka et al. 200 2009 298 whites GI = 0 Total sum of GI values at MMP‐9‐1562 The prevalence of MMP‐9‐1562 alleles was
Aged 11 to 13 years At all 24 examined sites 24 examined sites≥ 4 IL‐18‐607 significantly higher in G compared to H. A highly
(G = 147, H = 151) significant association of the composite genotype
(formed by the variants of both genes) with G
was found.
Garlet et al. 208 2012 608 whites and BOP score < 10% BOP > 70% IL1B‐3954 Positive associations were found for IL6‐174,
Afro‐American/ PD > 3 mm ≤ 1 tooth per sextant IL6‐174 IL10 ‐592 and TLR4‐299
Mulatto subjects CAL > 1 mm with CAL loss ≤1 mm TNFA‐308
(P = 197, G = 193, No history of tooth loss IL10 ‐592
H = 218) due to periodontitis TLR4‐299
a
BOP: bleeding on probing; CAL: clinical attachment level; gingival index; IL‐1: interleukin 1; IL‐1RA: interleukin 1 receptor antagonist; IL‐6: interleukin 6; IL‐10: interleukin 10; MMP‐9: matrix metallopro‐
teinase 9; TNF: tumor necrosis factor.
|
S59
genome‐wide association studies hold promise for the identification perception of a condition‐specific (CS) impact was limited to 27.1%
of genetic variations that are significantly associated with severe of subjects. Specificity with respect to individuals with no CS‐impact
gingival inflammation. 209 among periodontally healthy subjects was 0.83. Similarly, in a sam‐
Emerging evidence indicates that the inflammatory response ple of 1,100 12‐year old and 871 15‐year old Thai children, <30% of
may be modulated in a dynamic way by epigenetic processes, which subjects had CS‐impact on their quality of life related to gingivitis
are heritable and reversible. In particular, the modern concepts of and calculus despite the high prevalence (about 80%) of gingivitis
epigenetics imply that gene expression may be modified by environ‐ and/or calculus. The impact of gingivitis on children's OHRQoL was
mental exposures such as diet, microbial infections, cigarette smoke, mostly at low levels of extent and intensity. However, extensive
and diabetes. This implies that the genetic component of susceptibil‐ gingivitis was significantly associated with a moderate/higher level
ity to gingival inflammation could vary during post‐natal life, without of CS‐impacts.92 In a random sample of 1,134 12‐year‐old Brazilian
210
introduction of any mutations to a specific gene's DNA. Diseases schoolchildren, gingivitis extent showed an impact on OHRQoL,
such as cancer, initially identified as genetic, are now known to in‐ with mean quality of life scores being 1.15 higher for children with
volve both genetic and epigenetic abnormalities. 211 Even though ≥15% BOP+ sites than for children with < 15% BOP+ sites.93 Extent
pertinent studies are still limited in number, 212 it is reasonable to hy‐ of gingival bleeding (≥15% BOP) was significantly associated with
pothesize that epigenetic modulators will be evaluated in the future emotional well‐being, oral symptoms, functional limitations and so‐
for their potential impact on gingivitis. cial well‐being domains.93
In conclusion, when considering the pandemic distribution of Overall, data from these studies indicate that, although highly
gingivitis and its high prevalence in different populations, it can be prevalent, gingivitis has a limited impact on OHRQoL. However, gin‐
hardly expected that a GC definition can be based exclusively on givitis extent, in terms of BOP score, may increase the negative ef‐
genetic/epigenetic profiling/susceptibility, which currently remains fects on CS and general OHRQoL. Interestingly, an increasing level
to be determined. of agreement between the impact of gingivitis (CPI = 1 vs. CPI = 2)
on patient's quality of life and the presence of a normative need for
periodontal treatment has been reported. 224
Self‐reported diagnosis
Although studies on self‐assessment of oral health demonstrated
R E S U LT S A N D D I S CU S S I O N
the validity of self‐reporting on teeth present, decayed teeth, miss‐
ing teeth, malocclusion and prosthetic condition, studies on self‐as‐
The use of BOP to define and grade a GC
sessment of periodontal condition revealed inconsistent results with
varying levels of validity.7 When considering gingivitis, the most in‐ Based on available methods to assess gingival inflammation, a GC
91,213‒223
vestigated self‐reported symptom is “bleeding from gums”. could be simply, objectively and accurately defined and graded using
Several studies have validated self‐reported bleeding perception a BOP score (BOP%).40 A BOP score is assessed as the proportion of
91,217‒219,221,222
with BOP scores. Overall, findings seem to indicate bleeding sites (dichotomous yes/no evaluation) when stimulated by a
that self‐perceived bleeding (either spontaneous or evoked by dif‐ standardized (dimensions and shape) manual probe with a controlled
ferent mechanical stimulations) shows high specificity and low (∼25 g) force to the bottom of the sulcus/pocket at six sites (mesio‐
sensitivity. In the study by Schwarz,83 participants were asked “do buccal, buccal, disto‐buccal, mesio‐lingual, lingual, disto‐lingual) on
you have gum problems?”. Participants who self‐reported “no gum all present teeth.
problems” showed a gingival bleeding index (GBI) of 6.1%, those who BOP may be used for (i) discriminating between a healthy
self‐reported “gum problem often” showed a GBI of 24.5%. Baser and gingivitis patient, 35 and (ii) classifying a GC (localized, gen‐
91
et al. showed that 19 out of 20 dental students who presented eralized). 6 Use of BOP to identify a GC case would have the fol‐
with BOP < 10% reported no bleeding gums whereas about half of lowing advantages: 1) It is an objective, universally accepted,
the students with gingival bleeding (i.e. BOP > 10%) correctly identi‐ reliable and accurate clinical sign that may be easily assessed and
fied themselves as having gingival disease. In conclusion, the avail‐ recorded39,68,75‒79 as part of probing assessments necessary for
able data suggest that the self‐assessment of bleeding does not have a comprehensive periodontal examination; 2) Gingival bleeding
sufficient validity for screening individuals affected by gingivitis. represents a clinical sign often perceived by the patient, whereas
Interestingly, a limited number of bleeding sites (i.e. < 10%) appears low level of BOP% are consistent with self‐reported perception
to be associated with a self‐perception of periodontally‐healthy of healthy gingival conditions; 3) BOP recording is user‐friendly,
conditions. economic, and requires minimal/no technology. With suitable
training, it is possible for general dental practitioners to achieve
and maintain high levels of intra‐examiner consistency in assessing
Oral health‐related quality of life (OHRQoL)
bleeding;80 and 4) Bleeding score can be effectively used to inform
92,93,224
Few studies evaluated the impact of gingivitis on OHRQoL. and motivate the patient41,70,71,81 as well as monitor the efficacy of
224
In a cohort of 1,034 Thai children, Tsakos et al. showed that, while preventive and treatment strategies aimed to control periodontal
the prevalence of periodontal treatment need (CPI > 0) was 97%, the diseases. 82‒84
The authors are aware that BOP score is merely a measure of the TA B L E 7 Case definition of gingivitis in a reduced periodontium
extent of gingival inflammation rather than a method to assess the without history of periodontitis
severity of the inflammatory condition. The limitations arising from Localized gingivitis Generalized gingivitis
the use of semiquantitative indices, such as GI, to diagnose gingivitis
Probing Yes Yes
patients have been addressed above. Although severity of gingival attachment loss
inflammation may be well defined on a site‐specific basis,35 signs of
Radiographic bone Possible Possible
gingival inflammation, such as gingival volume and color changes (how‐ loss
ever assessed), can be hardly merged with BOP% at a patient‐level, and Probing depth (all ≤3 mm ≤3 mm
they would eventually result in a subjective, time consuming and im‐ sites)
practical procedure to establish a universally‐acceptable GC definition. BOP score ≥10%, ≤30% >30%
Beyond the underlying tissue inflammation, there are patient fac‐
tors that can affect the gingival response to mechanical stimulation
by a probe. Previous studies have clearly shown that the individual A patient with a reduced periodontium238 but without a history
tendency to develop gingival bleeding after probe stimulation may of periodontitis (e.g. gingival recession, crown lengthening) and a
be a host‐related trait that can depend on several patient‐related BOP score ≥10% would be diagnosed as a “GC on a reduced peri‐
factors.6,77,191 Smoking has been consistently shown to suppress the odontium”. A GC can also be graded as localized (BOP ≥10% and
89,225‒228
gingival bleeding response during development of gingivitis, ≤30%) or generalized (BOP > 30%) (Table 7).
while a limited number of studies have shown that under steady‐state The same criteria may also be applied to a patient with a reduced
conditions smoking increases the likelihood of a gingival bleeding re‐ periodontium238 who has been successfully treated for periodontitis
sponse to probing.229,230 Patients on anticoagulant medications (e.g., (periodontally stable patient), provided that no BOP positive sites
231‒234
aspirin) exhibit increased bleeding response to probing. Among show a probing depth ≥4 mm.
patients with similar ethnic background and plaque levels, differ‐ Both localized and generalized gingivitis should be managed by
ences in genetic background might also account for different BOP re‐ patient motivation, oral hygiene instruction, professional mechanical
sponses.191,198,201 Despite evidence suggesting a greater susceptibility plaque removal, and implementation of self‐performed mechanical
235,236
of thin gingival tissues to mechanical trauma, the significance of plaque control, which may be supplemented by adjunctive use of an‐
gingival quality/dimensions (i.e., periodontal phenotype) for the BOP timicrobial/anti‐inflammatory oral care products. Dietary advice and
response remains unresolved.230,237 Nevertheless, the presence of pa‐ tobacco counseling are recommended when indicated.
tient determinants known to affect the BOP response should be taken The proposed GC diagnostic criteria would be of great value
in consideration when determining the periodontal inflammatory con‐ for defining and monitoring the disease in an epidemiological
ditions, in general, and when diagnosing a GC, in particular. context, because such a GC definition should allow: 1) establish‐
ment of a framework that favors consistency of data interpreta‐
tion across global epidemiological studies; 2) calculation of odds
Definition of gingivitis in a patient with an intact
ratios and estimates of relative risk, both of which are sensitive
periodontium
to threshold definition, that are directly comparable between dif‐
A patient with an intact periodontium is diagnosed as a GC as fol‐ ferent studies; 3) assessment of the effectiveness of preventive
lows (Table 6): localized gingivitis, defined as a patient presenting measures and treatment regimens on a specific cohort of patients;
with a BOP score ≥10% and ≤30%, without attachment loss and ra‐ 4) establishment of priorities for large‐scale therapeutic actions/
diographic bone loss. This case may be associated with patient per‐ programs, with particular emphasis on their prognostic relevance
ception of bleeding gums, and a scarce, if any, impact on quality of (prevention of periodontitis) and impact on quality of life; and 5)
life; or generalized gingivitis, defined as a patient presenting with a undertaking of surveillance studies to monitor the prevalence and
BOP score > 30%, without attachment loss and radiographic bone distribution of gingivitis consistently within a cohort as well as
loss. This case is often associated with patient perception of bleed‐ among different populations. 34
ing gums, and a modest impact on quality of life. However, it might be considered that in daily practice a patient
with an intact periodontium or a reduced periodontium without
history of periodontitis who shows even one site with clinical signs
TA B L E 6 Case definition of gingivitis in an intact periodontium of gingival inflammation is worthy of professional intervention and,
therefore, should be considered as a patient with sites of gingivitis.
Localized gingivitis Generalized gingivitis
A direct implication of the proposed GC definition is that a
Probing attach‐ No No patient presenting with a BOP score < 10% without attachment
ment loss
loss and radiographic bone loss (intact periodontium) is con‐
Radiographic bone No No sidered clinically periodontally healthy. This definition is cor‐
loss
roborated by previous studies where a BOP < 10% was used to
BOP score ≥10%, ≤30% >30%
define a periodontally‐healthy case (Tables 3, 4, and 5).153,158,208
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How to cite this article: Trombelli L, Farina R, Silva CO,
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Received: 5 August 2016 | Revised: 18 April 2017 | Accepted: 8 May 2017
DOI: 10.1111/jcpe.12936
2017 WORLD WORKSHOP
Periodontal health
Niklaus P. Lang1 | P. Mark Bartold2
1
Universities of Bern and Zurich, Switzerland
2
Abstract
University of Adelaide, South Australia
Objectives: To date there is a paucity of documentation regarding definitions of peri‐
Correspondence
odontal health. This review considers the histological and clinical determinants of
Prof. Dr. Niklaus P. Lang, Professor Emeritus,
University of Bern, Scheuermattweg 33, periodontal health for both intact and reduced periodontium and seeks to propose
CH‐3043 Uettligen, Switzerland.
appropriate definitions according to treatment outcomes.
Email: [email protected]
Importance: Defining periodontal health is can serve as a vital common reference
point for assessing disease and determining meaningful treatment outcomes.
the Journal of Periodontology and Journal of Findings: The multifactorial nature of periodontitis is accepted, and it is recognized
that restoration of periodontal health will be defined by an individual's response to
treatment, taking into account allostatic conditions.
Conclusions: It is proposed that there are 4 levels of periodontal health, depending
on the state of the periodontium (structurally and clinically sound or reduced) and
the relative treatment outcomes: (1) pristine periodontal health, with a structurally
sound and uninflamed periodontium; (2) well‐maintained clinical periodontal health,
with a structurally and clinically sound (intact) periodontium; (3) periodontal disease
stability, with a reduced periodontium, and (4) periodontal disease remission/control,
with a reduced periodontium.
KEYWORDS
Clinical health, gingiva, periodontal remission, periodontal stability, pristine health
I NTRO D U C TI O N It is a matter of debate if altered morphological conditions result‐

ing from previous exposure to disease processes (eg, gingival reces‐
“Health is a state of complete physical, mental and social well‐being sion, loss of attachment, and bone loss) may be redefined as novel
1
and not merely the absence of disease or infirmity.” In accordance healthy conditions in the absence of clinical signs and symptoms of
with this definition by the World Health Organization, periodon‐ inflammation.
tal health should be defined as a state free from inflammatory Interestingly, there are almost no studies or reports attempting
periodontal disease that allows an individual to function normally to define periodontal health. 2 Defining periodontal health is very
and not suffer any consequences (mental or physical) as a result important if we are to have a common reference point for assess‐
of past disease. However, while this definition is holistic and pa‐ ing periodontal disease and determining meaningful treatment out‐
tient‐outcome based, it seems an impractical and limiting definition comes. Health can be evaluated at both the histological and clinical
for the purposes of clinical management of periodontal diseases. levels and should be considered in the context of a preventive start‐
Therefore, a more practical definition of periodontal health would ing point and a therapeutic end point. Thus, periodontal health can
be a state free from inflammatory periodontal disease. This, in turn, exist before disease commences but, conversely, periodontal health
means that absence of inflammation associated with gingivitis or can be restored to an anatomically reduced periodontium. In this
periodontitis, as assessed clinically, is a prerequisite for defining review, the clinical criteria for distinguishing pristine health from
periodontal health. health on a reduced periodontium are presented and discussed.
J Clin Periodontol. 2018;45(Suppl 20):S9–S16. wileyonlinelibrary.com/journal/jcpe | S9

S10 | LANG and BARTOLD
H I S TO LO G I C A L E V I D E N C E O F H E A LTH experimental gingivitis model in which oral hygiene practices

were abolished. 6 As the clinical index (gingival index) for inflam‐
Animal studies – pristine periodontal health and early
mation increased, the volumetric density of infiltrated connec‐
gingival inflammation
tive tissue within the noninfiltrated connective tissue in an area
During the 1970 and 1980s, various animal studies assessed the health subjacent to the junctional epithelium increased significantly and
3‒5
status of gingival tissues that were exposed to oral biofilms. These almost linearly.7 The infiltrated connective tissue demonstrated a
tissues were usually taken as baseline prior to commencement of significant increase in lymphocytes from health to inflammation
plaque accumulation for studies on the development and pathogenesis (17.0% to 29.9%) concomitant with a decrease in the numerical
of gingivitis. Clearly, most of the evidence for such healthy conditions density of fibroblasts, from 48.1% to 34.9%. Moreover, the nu‐
(homeostasis) was defined by a complete absence of inflammatory infil‐ merical density of polymorphonuclear leukocytes was between
trate concomitant with gingival and plaque indices, yielding zero values. 20.8% and 22.6% at all stages, from health to gingivitis. These
Histologically, composition of the gingival biopsies was analyzed results indicate that an inflammatory infiltrate subjacent to the
using a sampling microscope. It was stated that biopsies at day zero junctional epithelium is always present in gingival tissues that are
(commencement of plaque accumulation) did not contain any inflam‐ clinically healthy.
matory cell infiltrates. The original delicate vascular capillary net‐ To study the influence of long‐term gingival health, 5 dental hy‐
work of uninflamed gingival tissue has been described using vital gienists with optimal personal oral hygiene were supervised regard‐
microscopy, perfusion, and histological techniques in young dogs ing their oral hygiene performance for 6 months.8 It was assured that
and cats.4,5 However, after 4 days of plaque accumulation, a signifi‐ at all observation times (0, 1, 4, and 6 months) clinical indices for
cant number of leukocytes were found in the collagen‐poor connec‐ plaque and inflammation were close to zero. The volumetric den‐
tive tissue immediately beneath the junctional epithelium. The size sity of infiltrated connective tissue versus noninfiltrated connective
of the infiltrated connective tissue (ICT) gradually increased during tissue decreased significantly from month 1 to month 4. This indi‐
the experimental period and the volumetric density of collagen in cated that a long‐standing optimal oral hygiene regime is necessary
the noninfiltrated connective tissue (NCT) was always much higher for any histological improvement of the inflammatory infiltrate.
than in the ICT. In the ICT, however, collagen density remained con‐ Nevertheless, even after 6 months of supervised oral hygiene prac‐
stant throughout the study. By days 4 and 7, neutrophilic granulo‐ tices, the infiltrate was still present.8
cytes constituted 60% to 70% of the leukocyte population. On day While the numerical density of lymphocytes within the infiltrate
28, the infiltrate comprised mainly mononuclear leukocytes, espe‐ decreased significantly, from 18.4% to 5.6%, after 6 months of me‐
cially plasma cells; at that time neutrophils occupied only a small ticulous oral hygiene, the numerical density of fibroblasts increased
fraction of the infiltrate.3 significantly, from 57.7% to 71.0%. This clearly reflected a positive
The presence of biofilm and overt inflammation, occurring with healing outcome. However, it must be recognized that even during
eruption of deciduous teeth in dogs and cats, has been related to this 6 month period of optimal oral hygiene, the numerical density of
concomitant changes in gingival vascular morphology. Although lo‐ polymorphonuclear leukocytes remained relatively stable, varying
calized, acute inflammation accompanies biofilm formation at the from 20.6% to 17.7%. This, in turn, means that in humans a status
time of weaning, it rarely develops into a chronic inflammation. of clinically healthy gingiva, even for a prolonged period, is always
Infiltration of gingival tissue by chronic inflammatory cells occurred histologically characterized by a small inflammatory cell infiltrate.7,8
in only a few specimens and was associated with increased biofilm This indicates polymorphonuclear leukocyte surveillance, which is
and replacement of the gingival vessel network by loop patterns. a very important physiological (not pathological) process. Most re‐
This, in turn, meant the original delicate vascular network was re‐ cently, in human biopsies from clinically healthy sites, memory B
placed with loop configurations of capillaries once challenged by cells were identified within the connective tissue subjacent to the
biofilm‐induced inflammation.4 junctional epithelium. This suggests a role for memory B cells in
A subsequent study investigated whether the regular vascula‐ maintaining homeostasis.9
ture of noninflamed marginal gingiva would become re‐established Thus, the term pristine clinical health represents a rare, but re‐
following plaque control, scaling, and gingivectomy in dogs with alistic entity, ie, no attachment loss, no bleeding on probing (BoP),
and without pre‐experimental gingivitis at 4, 8, and 12 weeks.5 no sulcular probing >3 mm and no redness, clinical swelling/edema,
Noninflamed gingiva that was previously inflamed was characterized or pus. It should be recognized that this condition is associated
by a series of looped vessels that could be readily distinguished from with physiological immune surveillance rather than pathological
the regular network of vessels described for the marginal gingiva inflammation. The term clinically healthy should refer to tissue that
that had neither been inflamed nor resected previously.5 demonstrates an absence, or very low level, of clinical indicators
of inflammation such as BoP and inflammatory markers in gingival
crevicular fluid. This review did not consider gingival crevicular fluid
Human histological studies on health and gingivitis
biomarker research in periodontal health and disease, as crevicular
The cellular composition of developing infiltrated connective tis‐ fluid analysis is not generally practical to implement in clinical prac‐
sue was analyzed in human volunteers participating in a 21 day tice at this time due to the need for specialized equipment.
LANG and BARTOLD | S11
D E TE R M I N A NT S O F C LI N I C A L PL AQ U E A N D C LI N I C A L PE R I O D O NTA L
PE R I O D O NTA L H E A LTH H E A LTH
Subgingival biofilm
No longer can periodontal diseases be considered simple bacterial
infections. Rather, they are complex diseases of multifactorial nature The bacterial composition of the subgingival biofilm associated with
involving an intricate interplay between the subgingival microbiota, gingivitis and periodontitis results from dynamic interactions with
the host immune and inflammatory responses, and environmental its microenvironment. In general, the microbial composition is a col‐
modifying factors.10 Thus, periodontal health must not be consid‐ lection of commensal organisms that coexist in relative harmony.
ered solely in the context of plaque/bacteria levels and control but However, should the environment change, either as a result of in‐
must embrace a holistic consideration and evaluation of all factors flammation within the gingival tissues or other, as yet unidentified,
responsible for the emergence of disease, as well as the restoration processes within the biofilm, a state of dysbiosis may result in the
and maintenance of health.11 overgrowth of more virulent components of the biofilm, with en‐
Determinants of periodontal health fall into 3 major categories, suing exacerbation of periodontal inflammation.13 Thus, gingivitis
namely, microbiological, host, and environment (Table 1). Because can be considered a relatively nonspecific inflammatory response to
many of these factors are addressed in the paper dealing with plaque nonspecific (indigenous) subgingival microbiota. With the resultant
induced gingival diseases,12 we will only consider the clinical indica‐ inflammation and development of periodontitis, a shift in microbial
tors of clinical periodontal health in this article. composition occurs and several putative pathogens emerge, lead‐
The relevance of recognizing such important determinants ing to heightened host‐driven tissue damage. Thus, for periodontal
of periodontal health and disease as controllable and uncon‐ health to be attained, or maintained, the composition of the subgin‐
trollable predisposing and modifying factors cannot be under‐ gival microbiota needs to be redirected toward one compatible with
estimated, and their assessment for each patient is crucial to gingival health.14
attaining and maintaining clinical periodontal health. In this con‐
text, predisposing factors are defined as any agent or condition
Oral hygiene
that contributes to the accumulation of dental plaque (eg, tooth
anatomy, tooth position, restorations). Modifying factors are Good oral hygiene has always been considered a mainstay of peri‐
defined as any agent or condition that alters the way in which odontal health.15 It is usually achieved by a combination of good
an individual responds to subgingival plaque accumulation (eg, personal oral hygiene and regular professional care.16,17 It must be
smoking, systemic conditions, medications). The threshold(s) to remembered that plaque accounts for only 20% of the direct risk
establish when such factors are controlled versus not fully con‐ of developing periodontitis, thus it must not be forgotten that the
trolled await further elaboration, but it is reasonable to expect remaining 80% of direct and indirect risk and modifying factors may
that many factors will be determined controllable (eg, removal be responsible for the development of periodontal diseases.18 While
of overhangs, smoking cessation, good diabetes control) while oral hygiene remains the most important factor in obtaining and
others will not (eg, genetic predisposition, immune status, use of maintaining periodontal health, it should not be the sole focus of
critical medications). attention. Additional factors must be addressed in the quest for at‐
taining or maintaining periodontal health.
TA B L E 1 Determinants of clinical periodontal health
Microbiological Determinants of Clinical Periodontal Health

I N D I C ATO R S O F C LI N I C A L PE R I O D O NTA L
Supragingival plaque composition
H E A LTH
Subgingival biofilm composition
Host Determinants of Clinical Periodontal Health
In its pristine form, periodontal health would be defined as the
1. Local predisposing factors
absence of histological evidence of periodontal inflammation and
1.1 Periodontal pockets
1.2 Dental restorations no evidence of anatomical change to the periodontium. However,
1.3 Root anatomy it must be recognized that in most (if not all) adults this is unlikely.
1.4 Tooth position and crowding Therefore, the term clinically healthy should be adopted to cover
2. Systemic modifying factors
the absence of (or very significant reduction in) clinical periodon‐
2.1 Host immune function
2.2 Systemic health
tal inflammation on either an anatomically intact periodontium or
2.3 Genetics a reduced periodontium. Furthermore, a compromised definition
Environmental Determinants of Clinical Periodontal Health or paradigm for periodontal clinical health needs to be developed
Smoking for individuals who have experienced periodontal disease (gingivitis

Medications or periodontitis), undergone treatment, then returned to a state of
Stress clinical health on either a full periodontium (in the case of gingivitis)
Nutrition
or a reduced periodontium (in the case of periodontitis).
appears the most reliable for monitoring patients in daily practice over
Bleeding on probing
time.24,25 Nonbleeding sites may be considered as clinically healthy
Monitoring health or inflammation of the gingival tissues is best and periodontally stable. It would be logical to assume that the posi‐
documented by the parameter of BoP.19 Bleeding on probing, in the tive outcomes of periodontal treatment, in receptive patients, would
absence of pocketing, should be understood as bleeding provoked reach a status of nonbleeding on gentle probing.
in the coronal marginal gingiva following the application of pressure Because various factors, such as probe dimension, angulation of
to the lateral wall of a periodontal sulcus or pocket, reflecting micro‐ probe, and applied pressure, can affect the assessment of gingival
ulceration of the sulcus lining. However, BoP is usually measured as inflammation, it is imperative to standardize BoP as resulting from
bleeding provoked by applying a probe to the bottom of a sulcus/ a defined level of force (pressure to the tissue), preferably not ex‐
pocket. In most studies on BoP as a clinical parameter, this latter ceeding 0.25 N. 26
definition is applied. The histological characteristics of the gingival A multilevel analysis of various site‐specific and patient‐related
tissues associated with BoP have been evaluated. 20 Sites that bleed factors influencing BoP in 601 adult patients demonstrated that
following probing with light pressure applied to the tissues (0.25 N) BoP may be associated with site‐specific factors (periodontal prob‐
are associated with a significantly increased percentage of cell‐rich ing depth [PPD], tooth type, and aspects) as well as patient‐related
and collagen‐reduced connective tissue but no increase in vascular‐ factors (eg, sex and smoking status). 27 While the severity and extent
ity or vessel lumen size that would justify the bleeding tendency. of gingival bleeding are often associated with the degree of bacte‐
Moreover, clinical and histological data suggest that bleeding is an rial plaque accumulation, it is noted that other factors can lead to
earlier sign of gingivitis than are the visual signs of inflammation increased gingival bleeding. For example, vitamin C deficiency or
(redness and swelling). ingestion of aspirin can cause significant gingival bleeding through
Obviously, BoP may be provoked by trauma to the tissues using mechanisms that may not be primarily related to plaque accumula‐
a periodontal probe. Hence, the probing pressure to be applied to tion. 28,29 In a recent retrospective study of 445 patients in periodon‐
the tissue (bottom of the sulcus/pocket) when evaluating BoP should tal supportive therapy for at least 5 years, increased mean BoP in
not be sufficient to create trauma; rather it should only be enough patients on supportive periodontal therapy was related to disease
to provoke tissue to bleed if there is increased blood vessel fragil‐ severity and periodontal instability irrespective of smoking status;
ity resulting from inflammation. It has been demonstrated that BoP smokers demonstrated lower mean BoP concomitant with increased
provoked with pressures greater than 0.25 N results in false‐pos‐ prevalence of residual PPD.30
itive readings. By incrementally increasing pressure by 0.25 N, an
increase of approximately 13% in BoP sites has been noted. 21,22
Standardization of periodontal probe design
An early retrospective study evaluated the prognostic value of
BoP compared with repeated visits in identifying sites at risk for The characteristics of an ideal periodontal probe will be central to a
periodontal attachment loss during supportive care following peri‐ future determination of periodontal health. There is need to develop
odontal therapy. 23 The results indicated that sites with a probing an International Organization for Standardization periodontal probe
depth of ≥5 mm had significantly higher incidence of BoP. Sites with to ensure not only that probe dimension is consistent but that prob‐
an incidence of BoP at 4 of 4 visits had a 30% chance of attachment ing force is standardized to 0.25 N, thus removing the confounding
loss. This decreased to 14% with an incidence of BoP at 3 of 4 visits, issue of BoP induced by too much pressure, as well as unneces‐
to 6% with an incidence of BoP at 2 of 4 visits, to 3% with an inci‐ sary bleeding resulting from trauma. This critical issue is discussed
dence of BoP at 1 of 4 visits, and finally, to 1.5% with no BoP at any in more detail by Trombelli and Tatakis (fourth paper for Working
of 4 visits. Sensitivity and predictability calculations revealed that Group 1; in this issue).31
BoP is a limited but useful prognostic indicator in monitoring peri‐
odontal tissue after active therapy. 23
Periodontal probing depth
Subsequent studies investigated the predictive value of absence
of BoP as an indicator for periodontal stability. 24,25 While the pos‐ While it would seem intuitive that shallow pockets are consistent
itive predictive value remained rather low for repeated BoP preva‐ with health and deep pockets consistent with disease, there is ample
lence (≤30%), the negative predictive value in the same studies was evidence to indicate this may not necessarily be true. For example,
nearly 100%. This demonstrated that absence of BoP at repeated deep pockets may remain stable and uninflamed, particularly if care‐
examinations represented periodontal health and was a very reliable ful supportive periodontal care is provided, over very long periods of
indicator for periodontal stability. 24 Hence, from a clinical point of time.32,33 Thus, deep pockets may exist as so‐called healthy pockets.
view, absence of BoP would indicate clinically healthy periodontal It is important to recognize that, following successful treatment,
tissue. These findings were later validated in a prospective follow‐up recurrent inflammatory periodontitis can recur at individual sites de‐
study applying BoP as a clinical indicator for disease progression or spite most of the dentition remaining well maintained and in a state
periodontal stability. 25 of relative health.33 This has been interpreted to indicate that mean
As the absence of BoP at 0.25 N indicates periodontal health, with values of clinical parameters such as PPD, attachment levels, and
a negative predictive value of 98% to 99%, this clinical parameter bone height are not adequate predictors for sites that may become
reinfected and undergo recurrent disease.33 Thus, PPD or probing the periodontium may be completely healthy. If the height of the
attachment levels alone should not be used as evidence of gingi‐ periodontal support is reduced but the width of the ligament is un‐
val health or disease. They must be considered in conjunction with changed (approximately 250 μm), it should be appreciated that the
other important clinical parameters such as BoP, as well as modifying amplitude of root mobility within the remaining periodontium is
and predisposing factors. This highlights, as stated above, that the the same as for a tooth with normal height of periodontal support.
most useful indicator of disease is clinical evidence of inflammation, Hence, the so‐called hypermobility of a periodontally healthy tooth
and that historical evidence of disease (increased PPD, recession and with reduced support but normal width of periodontal ligament
loss of attachment, bone loss) may be of less relevance in the context should be considered physiological tooth mobility.
of periodontal health on a reduced periodontium.34 Increased tooth mobility due to a widening in the periodontal
ligament is the result of uni‐ or multidirectional forces to the crown
that are sufficiently high and frequent to induce resorption of the
Radiographic features of periodontal health
alveolar bone walls in pressure zones. In a series of controlled ani‐
Radiographic assessment forms a critical component of clini‐ mal experimental studies in periodontally healthy teeth, the alveolar
cal assessment of the periodontium. Radiographic features of a bone resorption resulted in increased tooth mobility but no loss of
normal, anatomically intact periodontium would include an intact connective tissue attachment, irrespective of the height of the sup‐
lamina dura (both laterally and at the alveolar crest), no evidence portive bone.38,39 Because alveolar bone loss has been demonstrated
of bone loss in furcation areas, and a 2 mm distance, on average, to be reversible upon cessation of applied forces, it was concluded
from the most coronal portion of the alveolar bone crest (AC) to that increased tooth mobility as a result of a widened periodontal
the cementoenamel junction (CEJ). The distance from the CEJ to ligament represents a physiological adaptation to altered function
AC in healthy individuals can vary between 1.0 and 3.0 mm. 35,36 It rather than a sign of pathology.37 Hence, tooth mobility is not rec‐
is important to note that factors such as patient age, tooth type, ommended to be used as a sign of either health or disease status.
angulation of teeth, and severe attrition can all influence the CEJ‐
AC height, thus caution must be exercised when assessing this
parameter as a measure of periodontal health. While periodontal PE R I O D O NTA L H E A LTH A N D TR E ATM E NT
ligament space is also appraised radiographically, it can vary and is TA RG E T S FO R A D I S E A S E D O R R E D U C E D
not considered a useful indicator of health (see section below on PE R I O D O NTI U M
tooth mobility).
Once periodontitis has developed, by definition, alveolar bone While maintaining periodontal health over a lifetime with no adverse
loss has occurred because of the inflammatory process. Thus, clini‐ changes in the periodontium is desirable, it must be recognized this
cal periodontal health on a reduced periodontium cannot be deter‐ is unlikely for most of the population.
mined using radiographs alone; they provide information regarding In Table 2, periodontal conditions and their expected outcomes
historical destruction and are of value for longitudinal determination with respect to periodontal health are detailed within the context
of progressive bone loss. of an intact and a reduced periodontium. For the treatment of gin‐
givitis, it is not realistic to return to pristine periodontal health;
restoration to full clinical health (no BoP, no anatomical loss of peri‐
Tooth mobility
odontal structures) would be expected following removal of biofilm
Clinicians often assess the status of a tooth by estimating its mobility. and calculus and ongoing effective oral hygiene and maintenance.
Because teeth are not ankylosed, or osseointegrated, as are implants, In treating periodontitis, which by definition manifests as loss of
but are suspended in the alveolar bone by a network of collagenous periodontal support (both attachment and bone), restoration to
fibers, they exhibit a degree of physiological mobility. This is usually pre‐disease attachment and bone levels is an unlikely event at the
assessed as the amplitude of crown displacement resulting from the majority of sites; therapeutic targets are to control local and mod‐
37
application of a defined force. The magnitude of this movement ifying factors, minimize inflammation, and stabilize attachment and
has been used to distinguish between physiological and pathological bone. Therefore, for a large proportion of the population, the issue
tooth mobility, with up to 0.2 mm regarded as physiological. In teeth of periodontal health must be considered in the context of returning
with noninflamed periodontal tissue, 2 fundamental histological fac‐ to clinical health from disease (either gingivitis or periodontitis) and
tors determine tooth mobility: 1) the height of the periodontal tissue what this return entails. According to recent epidemiological data,
support and 2) the width of the periodontal ligament. gingivitis affects up to 95% of the population and chronic periodon‐
In a clinically healthy situation, increased tooth mobility asso‐ titis up to 60% to 65% of the North American population 65 years
ciated with widening of the periodontal ligament most likely rep‐ and older.40,41 While some variance is to be expected across com‐
resents a tooth in occlusal trauma. Furthermore, increased tooth munities, these figures are likely to be relatively accurate for most
mobility cannot be used as a sign of disease for a tooth with a re‐ populations worldwide.
duced, but healthy, periodontium. Such increased mobility may be In the context of our current understanding of the multifacto‐
permanently increased due to reduced periodontal support, yet rial nature of (plaque‐associated) periodontal diseases, reducing
TA B L E 2 Outcomes of periodontal health for plaque‐associated periodontal diseases
Periodontitis (reduced periodontium)
Pristine
periodontal Clinical periodontal health Periodontal Periodontal disease
health (intact periodontium) Gingivitis disease stability remission/control
Bleeding on No No/Minimal Yes No/Minimal Significantly reduced

probing
Normal gingival Yes Yes Yes No No
sulcus depth
Normal bone Yes Yes Yes No No
heights
Modifying factors Controlled Controlled May be present Controlled Not fully controlled
Predisposing Controlled Controlled May be present Controlled Not fully controlled
factors
Pristine periodontal health is defined as no bleeding on probing and no anatomical loss of periodontal structures. Gingivitis is defined as a nonspe‐
cific inflammatory reaction to a nonspecific accumulation of plaque that is confined to the gingival tissue, with no underlying destruction of the
attachment apparatus. Periodontitis covers the major plaque‐associated periodontal diseases, and treatment outcomes are expected to be either
periodontal disease stability or periodontal disease remission/control. Periodontal disease stability is defined as a state in which the periodontitis has
been successfully treated and clinical signs of the disease do not appear to worsen in extent or severity despite the presence of a reduced perio‐
dontium. Periodontal disease remission/control is defined as a period in the course of disease when symptoms become less severe but may not be
fully resolved.
inflammation and improving clinical health for a reduced periodon‐ is related to the achievement of other (ie, different from those ob‐
tium may be achieved at 2 levels, namely stability and remission/ tained in the disease stability definition) treatment end points that
control. These are variants of therapeutic outcomes to restore testify to an improvement in periodontal condition (with respect to
health on a reduced periodontium. baseline status) that, if not achieved, may be associated with pro‐
Periodontal disease stability will be defined as a state in which gression of attachment loss.
periodontitis has been successfully treated through control of If the concept of disease remission/control is embraced as a
local and systemic factors, resulting in minimal BoP, optimal im‐ treatment target for the management of periodontal diseases, peri‐
provements in PPD and attachment levels, and a lack of progres‐ odontal treatment will move from a solely biofilm‐based protocol to
sive destruction. The principal signs of successful periodontal a more holistic, inflammation‐based model. It is important to note
treatment would be as detailed above with regard to BoP, PPD, that this model does not discount or diminish the importance of the
and clinical attachment levels. In addition, control of modifying periodontal microbiome, but refocuses attention on controlling the
factors such as reduction of daily cigarette smoking and good inflammation to control the infection and the ongoing destruction of
control of diabetes are achieved. In many respects, attainment the periodontium.
of periodontal disease stability can be considered a prognostic This model requires that modifiable indicators of periodontitis
definition. such as traditional markers of periodontitis (attachment and bone
Periodontal disease remission/control is defined as a period in the loss and PPD), modifiable inflammatory markers (periodontal in‐
course of disease during which treatment has resulted in reduction flammation score, inflammatory mediators in gingival crevicular
(although not total resolution) of inflammation and some improve‐ fluid) and modifiable systemic risk factors (eg, diabetes, smok‐
ment in PPD and attachment levels, but not optimal control of local ing) be accounted for when evaluating the outcome of periodon‐
or systemic contributing factors. This may be a reasonable treat‐ tal treatment and whether there has been a positive response to
ment outcome for individuals with uncontrollable modifying factors. treatment consistent with progression toward periodontal health
Indeed for many chronic inflammatory medical conditions (eg, diabe‐ and stability. Thus, specific measurable biological and clinical out‐
tes, cardiovascular disease, hyperlipidemia, and rheumatoid arthri‐ comes should be determined to form the basis for assessment of
tis), the goal of disease remission is important and is based on the periodontal health based largely (but not exclusively) on the in‐
emerging concept of treat to target.42 This is a treatment paradigm flammatory response.
that utilizes specific and well‐defined treatment outcomes to moni‐
tor the control of the clinical signs and symptoms of a disease and is
aimed at attaining a state of putative health. For patients with long‐ CO N C LU S I O N S
standing disease and/or uncontrolled contributing factors, for exam‐
ple smoking or diabetes, low disease activity may be an acceptable It is proposed that there are 4 levels of periodontal health, depend‐
therapeutic goal. Thus, the definition of disease remission/control ing upon whether the periodontium has normal attachment and
bone level or reduced support, as well as the ability to control modi‐ 10. Bartold PM. Van Dyke TE. Periodontitis: a host‐mediated disruption
fying factors and relative treatment outcomes. These 4 categories of microbial homeostasis. Unlearning learned concepts. Periodontol
2000. 2013;62:203–217.
include 1) pristine periodontal health, defined as a total absence of
11. Zaura E, ten Cate JM. Towards understanding oral health. Caries
clinical inflammation and physiological immune surveillance on a Res. 2015;49(Suppl 1):55–61.
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Pristine periodontal health is not likely to be observed clinically; duced gingival conditions. J Clin Periodontol. 2018;45(Suppl 20):S17–S27.
13. Darveau RP, Hajishengallis G, Curtis MA. Porphyromonas gingi-
2) clinical periodontal health, characterized by an absence or mini‐
valis as a potential community activist for disease. J Dent Res.
mal levels of clinical inflammation in a periodontium with normal 2012;91:816–820.
support; 3) periodontal disease stability in a reduced periodontium; 14. Teles FR, Teles RP, Uzel NG, et al. Early microbial succession in
4) periodontal disease remission/control in a reduced periodontium. redeveloping dental biofilms in periodontal health and disease. J
Periodontal Res. 2012;47:95–104.
Periodontal disease stability and periodontal disease remission/
15. Tonetti MS, Eickholz P, Loos BG, et al. Principles in prevention
control are differentiated based on the ability to control modifying of periodontal diseases: consensus report of group 1 of the 11th
factors and therapeutic response. Stability is characterized by mini‐ European Workshop on Periodontology on Effective Prevention
mal inflammation and optimal therapeutic response, with control of of Periodontal and Peri‐Implant Diseases. J Clin Periodontol.
2015;42(Suppl 16):S5–S11.
modifiable risk factors; it is a major treatment goal for periodontitis.
16. Axelsson P, Lindhe J. Effect of controlled oral hygiene procedures
For patients in whom it is not possible to fully control modifying and
on caries and periodontal disease in adults. Results after 6 years. J
predisposing factors, remission/control may be the more realisti‐ Clin Periodontol. 1981;8:239–248.
cally achievable therapeutic goal. Remission/control is character‐ 17. Axelsson P, Lindhe J. The significance of maintenance care in
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281–294.
other clinical parameters, and a stabilization of disease progression.
18. Grossi SG, Zambon JJ, Ho AW, et al. Assessment of risk for peri‐
Ideally, restoration to periodontal stability should be a major treat‐ odontal disease. I. Risk indicators for attachment loss. J Periodontol.
ment goal and can be attained by controlling inflammation and infec‐ 1994;65:260–267.
tion, reducing predisposing factors, and controlling any modifying 19. Lang NP, Joss A, Tonetti MS. Monitoring disease during supportive
periodontal treatment by bleeding on probing. Periodontol 2000.
factors. While remission/control should be a clear target, based on
1996;12:44–48.
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native therapeutic goal, particularly in long‐standing disease. nosis of periodontal disease. A literature review. J Periodontol.
1984;55:684–688.
21. Lang NP, Nyman S, Senn C, Joss A. Bleeding on probing as it re‐
lates to probing pressure and gingival health. J Clin Periodontol.
AC K N OW L E D G M E N T S A N D D I S C LO S U R E S
1991;18:257–261.
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This review has been supported by the Clinical Research Foundation
relates to probing pressure and gingival health in patients with a re‐
(CRF) for the Promotion of Oral Health, Brienz, Switzerland. The au‐ duced, but healthy periodontium. A clinical study. J Clin Periodontol.
thors declare they have no conflicts of interest related to this review. 1992;19:471–475.
23. Lang NP, Joss A, Orsanic T, Gusberti FA, Siegrist BE. Bleeding on
probing. A predictor for the progression of periodontal disease. J
Clin Periodontol. 1986;13:590–596.
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Aim and The aim of the Journal of Clinical Periodontology is to provide the platform for exchange of scientific and clinical progress in the field of
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Journal of Clinical Periodontology Ć Vol. 45 Supplement 20 June 2018
Contents
INTRODUCTION
A new classification scheme for periodontal and peri-implant S1 J. G. Caton, G. Armitage, T. Berglundh,
diseases and conditions – Introduction and key changes from I. L. Chapple, S. Jepsen, K. S. Kornman,
the 1999 classification B. L. Mealey, P. N. Papapanou, M. Sanz
and M. S. Tonetti
WORKGROUP 1: PERIODONTAL HEALTH AND

GINGIVAL DISEASES AND CONDITIONS
Periodontal health S9 N. P. Lang and P. M. Bartold
Dental plaque–induced gingival conditions S17 S. Murakami, B. L. Mealey, A. Mariotti and
I. L. Chapple
Non–plaque-induced gingival diseases S28 P. Holmstrup, J. Plemons and J. Meyle
Plaque-induced gingivitis: Case definition and diagnostic S44 L. Trombelli, R. Farina, C. O. Silva and D. N. Tatakis
considerations
Periodontal health and gingival diseases and conditions on S68 I. L. Chapple, B. L. Mealey, T. E. Van Dyke,
an intact and a reduced periodontium: Consensus report P. M. Bartold, H. Dommisch, P. Eickholz,
of workgroup 1 of the 2017 World Workshop on the M. L. Geisinger, R. J. Genco, M. Glogauer,
Classification of Periodontal and Peri-Implant Diseases and M. Goldstein, T. J. Griffin, P. Holmstrup,
Conditions G. K. Johnson, Y. Kapila, N. P. Lang, J. Meyle,
S. Murakami, J. Plemons, G. A. Romito, L. Shapira,
D. N. Tatakis, W. Teughels, L. Trombelli, C. Walter,
G. Wimmer, P. Xenoudi and H. Yoshie
WORKGROUP 2: PERIODONTITIS
Acute periodontal lesions (periodontal abscesses and S78 D. Herrera, B. Retamal-Valdes, B. Alonso and
necrotizing periodontal diseases) and endo-periodontal lesions M. Feres
Classification and diagnosis of aggressive periodontitis S95 D. H. Fine, A. G. Patil and B. G. Loos
Mean annual attachment, bone level, and tooth loss: S112 I. Needleman, R. Garcia, N. Gkranias,
A systematic review K. L. Kirkwood, T. Kocher, A. D. Iorio, F. Moreno
and A. Petrie
Age-dependent distribution of periodontitis in two countries: S130 M. Billings, B. Holtfreter, P. N. Papapanou,
Findings from NHANES 2009 to 2014 and SHIP-TREND 2008 G. L. Mitnik, T. Kocher and B. A. Dye
to 2012
Staging and grading of periodontitis: Framework and proposal S149 M. S. Tonetti, H. Greenwell and K. S. Kornman
of a new classification and case definition
Periodontitis: Consensus report of workgroup 2 of the 2017 S162 P. N. Papapanou, M. Sanz, N. Buduneli, T. Dietrich,
World Workshop on the Classification of Periodontal and Peri- M. Feres, D. H. Fine, T. F. Flemmig, R. Garcia,
Implant Diseases and Conditions W. V. Giannobile, F. Graziani, H. Greenwell,
D. Herrera, R. T. Kao, M. Kebschull, D. F. Kinane,
K. L. Kirkwood, T. Kocher, K. S. Kornman,
P. S. Kumar, B. G. Loos, E. Machtei, H. Meng,
A. Mombelli, I. Needleman, S. Offenbacher,
G. J. Seymour, R. Teles and M. S. Tonetti
WORKGROUP 3: PERIODONTAL MANIFESTATIONS
OF SYSTEMIC DISEASES AND DEVELOPMENTAL AND
ACQUIRED CONDITIONS
Manifestations of systemic diseases and conditions that affect S171 J. M. Albandar, C. Susin and F. J. Hughes
the periodontal attachment apparatus: Case definitions and
diagnostic considerations
Mucogingival conditions in the natural dentition: Narrative S190 P. Cortellini and N. F. Bissada
review, case definitions, and diagnostic considerations
Occlusal trauma and excessive occlusal forces: Narrative S199 J. Fan and J. G. Caton
review, case definitions, and diagnostic considerations
Dental prostheses and tooth-related factors S207 C. Ercoli and J. G. Caton
Periodontal manifestations of systemic diseases and S219 S. Jepsen, J. G. Caton, J. M. Albandar,
developmental and acquired conditions: Consensus report N. F. Bissada, P. Bouchard, P. Cortellini, K. Demirel,
of workgroup 3 of the 2017 World Workshop on the M. de Sanctis, C. Ercoli, J. Fan, N. C. Geurs,
Classification of Periodontal and Peri-Implant Diseases and F. J. Hughes, L. Jin, A. Kantarci, E. Lalla,
Conditions P. N. Madianos, D. Matthews, M. K. McGuire,
M. P. Mills, P. M. Preshaw, M. A. Reynolds,
A. Sculean, C. Susin, N. X. West and K. Yamazaki
WORKGROUP 4: PERI-IMPLANT DISEASES AND

CONDITIONS
Peri-implant health S230 M. G. Araujo and J. Lindhe
Peri-implant mucositis S237 L. J. A. Heitz-Mayfield and G. E. Salvi
Peri-implantitis S246 F. Schwarz, J. Derks, A. Monje and H. Wang
The etiology of hard- and soft-tissue deficiencies at dental S267 C. H. F. Hämmerle and D. Tarnow
implants: A narrative review
Peri-implant health, peri-implant mucositis, and S278 S. Renvert, G. R. Persson, F. Q. Pirih and
peri-implantitis: Case definitions and diagnostic considerations P. M. Camargo
Peri-implant diseases and conditions: Consensus report S286 T. Berglundh, G. Armitage, M. G. Araujo,
of workgroup 4 of the 2017 World Workshop on the G. Avila-Ortiz, J. Blanco, P. M. Camargo, S. Chen,
Classification of Periodontal and Peri-Implant Diseases and D. Cochran, J. Derks, E. Figuero, C. H. F. Hämmerle,
Conditions L. J. A. Heitz-Mayfield, G. Huynh-Ba, V. Iacono,
K.-T. Koo, F. Lambert, L. McCauley, M. Quirynen,
S. Renvert, G. E. Salvi, F. Schwarz, D. Tarnow,
C. Tomasi, H. Wang and N. Zitzmann
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Received: 4 October 2016 | Revised: 29 June 2017 | Accepted: 30 July 2017
DOI: 10.1111/jcpe.12941
2017 WORLD WORKSHOP
Acute periodontal lesions (periodontal abscesses and

necrotizing periodontal diseases) and endo‐periodontal lesions
David Herrera1 | Belén Retamal‐Valdes2 | Bettina Alonso1 | Magda Feres2
1
ETEP (Etiology and Therapy of Periodontal
Diseases) Research Group, University Abstract
Complutense, Madrid, Spain Objective: To critically evaluate the existing literature on acute lesions occurring in
2
Department of Periodontology, Dental
the periodontium (periodontal abscesses [PA], necrotizing periodontal diseases
Research Division, Guarulhos University,
Guarulhos, São Paulo, Brazil [NPD], and endo‐periodontal lesions [EPL]) to determine the weight of evidence for
the existence of specific clinical conditions that may be grouped together according
Correspondence
Prof. David Herrera, Facultad de to common features. The ultimate goal is to support an objective classification
Odontología, Plaza Ramón y Cajal s/n
system.
(Ciudad Universitaria), 28040 Madrid, Spain.
Email: [email protected] Importance: Although PA, NPD, and EPL occur with relatively low frequency, these
lesions are of clinical relevance, because they require immediate management and
jointly and simultaneously published in might severely compromise the prognosis of the tooth.
the Journal of Periodontology and Journal of Findings: In general, the evidence available to define these three conditions was con‐
Clinical Periodontology
sidered limited. PA and EPL are normally associated with deep periodontal pockets,
bleeding on probing, suppuration, and almost invariably, with pain. EPL are also as‐
sociated with endodontic pathology. NPDs have three typical features: pain, bleed‐
ing, and ulceration of the gingival interdental papilla. The available data suggested
that the prognosis of PA and EPL are worse in periodontitis than in nonperiodontitis
patients. Lesions associated with root damage, such as fractures and perforations,
had the worst prognosis. NPD progression, extent and severity mainly depended on
host‐related factors predisposing to these diseases.
Conclusions: PA should be classified according to the etiological factors involved,
with the most frequent being those occurring in pre‐existing periodontal pockets.
NPD are clearly associated with the host immune response, which should be consid‐
ered in the classification system for these lesions. EPLs should be classified according
to signs and symptoms that have direct impact on their prognosis and treatment,
such as presence or absence of fractures and perforations, and presence or absence
of periodontitis.
KEYWORDS
endo‐periodontal lesions, necrotizing gingivitis, necrotizing periodontal diseases, necrotizing
periodontitis, periodontal abscess
According to the American Academy of Periodontology,1 acute peri‐ pain or discomfort, tissue destruction, and infection. Among these
odontal diseases are rapid‐onset clinical conditions that involve the conditions, the following diseases have been listed: gingival abscess,
periodontium or associated structures and may be characterized by periodontal abscess, necrotizing periodontal diseases, herpetic

HERRERA et al. | S79
gingivostomatitis, pericoronal abscess, or pericoronitis, and com‐ NPD and 74 for EPL. Details about the electronic search methods
bined periodontal‐endodontic lesions. Herpetic gingivostomatitis and studies included, flow charts showing the selection of articles
is not included in the present review, whereas the so called gingi‐ for each condition evaluated in this review, and designs of the stud‐
val and periodontal abscesses were considered within a category ies included are described in Appendices 1 and 2, respectively, in the
named: abscesses in the periodontium (Figure 1). online Journal of Clinical Periodontology.
Acute lesions in the periodontium are among the few clinical
situations in periodontics in which patients may seek urgent care,
1 | PE R I O D O NTA L A B S C E S S E S
mostly because of the associated pain. In addition, and in contrast to
most other periodontal conditions, rapid destruction of periodontal
1.1 | Clinical presentation
tissues may occur during the course of these lesions, thus emphasiz‐
ing the importance of prompt diagnosis and treatment. The present Different etiological factors may explain the occurrence of abscesses
review and update focuses on two acute conditions (abscesses in the in the periodontal tissues, such as pulp necrosis (endodontic, peri‐
periodontium and necrotizing periodontal diseases); and on endo‐ apical or dentoalveolar abscesses), periodontal infections (gingival
periodontal lesions that can occur in acute or chronic forms. or periodontal abscess5), pericoronitis (pericoronal abscess), trauma,
Periodontal abscesses (PA) are important because they repre‐ surgery,6 or foreign body impaction. Together, they are referred to
sent common dental emergencies requiring immediate management as odontogenic or dental abscesses,7 and when they are associated
and can result in rapid destruction of the periodontium with a nega‐ with EPL, they could also be considered odontogenic abscesses. PA
tive impact on the prognosis of the affected tooth. In certain circum‐ can specifically be defined as a localized accumulation of pus located
stances, PA may have severe systemic consequences. 2,3 Although within the gingival wall of the periodontal pocket, with an expressed
the prevalence of necrotizing periodontal diseases (NPD) is low, periodontal breakdown occurring during a limited period of time, and
their importance is clear, because they represent the most severe with easily detectable clinical symptoms.2
conditions associated with dental biofilm, leading to very rapid tis‐ Three different reasons could support the importance of PA:
sue destruction.3 Whereas, endo‐periodontal lesions (EPL), in spite
of being relatively rare in clinical practice, might severely compro‐ Common dental emergencies, requiring immediate management (see
mise the prognosis of the tooth, and are considered one of the most Appendix 3, Table A3.1, in online journal)
challenging problem faced by clinicians, because they require multi‐
disciplinary evaluation, diagnosis, and treatment.4 a. PA represented approximately 7.7–14.0% of all dental emergencies,
The aim of the present review was to critically evaluate the ex‐ being ranked the third most prevalent infection demanding emer‐
isting literature on acute lesions in the periodontium (PA and NPD) gency treatment, after dentoalveolar abscesses and pericoronitis.
and EPL, with the purpose of determining the weight of evidence In an army dental clinic, 27.5% of periodontitis patients presented
of the existence of specific clinical conditions that may be grouped with PA, with clear differences between patients undergoing ac‐
together according to common features. The ultimate goal was to tive periodontal treatment (13.5%) and untreated patients (59.7%).8
support an objective classification system that may help the clini‐ Among patients undergoing periodontal maintenance (PeM), PAs
cian to determine the prognosis of the teeth involved, and treatment were detected in 37% of the patients followed‐up for 5–29 years.9
of these conditions. To achieve this objective, the three conditions In the Nebraska prospective longitudinal study, 27 PA were observed
were separately assessed. during 7 years, and 23 of them occurred in sites that received coronal
scaling.10
b. Rapid destruction of periodontal tissues, with a negative effect on the
M E TH O D S prognosis of the affected tooth (see Appendix 3, Table A3.1, in on‐
line journal)
Independent electronic searches were conducted to identify rel‐ PAs may lead to tooth loss, especially if they affect teeth with
evant articles dealing with each of the three conditions addressed previous moderate to severe attachment loss, as occur during
in this review. In total, 128 studies were included for PA, 138 for PeM in patients with severe chronic periodontitis. Indeed, they
1
Virus
Other abscesses Odontogenic or dental abscesses7
Endo-perio Periodontal
gingivostomat Surgery6 Trauma6 6,5,1 Pulp necrosis
6,1 lesion6,1 6,5,1
gingivis
Dentoalveolar Endo-perio Gingival Periodontal
Out of the Out of the Out of the Out of the abscess abscess abscess abscess
scope scope scope scope Out of the
Part 3. Part 1. Part 2.
scope
FIGURE 1 List of “acute periodontal conditions,” according to different authors, and scope of the present review
S80 | HERRERA et al.
have been considered the main cause of tooth extraction during normal oral epithelium and lamina propria; an acute inflammatory in‐
9,11‒13
PeM. Similarly, teeth with repeated abscess formation were filtrate; intense focus of inflammation, with presence of neutrophils
considered to have a “hopeless prognosis”,14 and 45% of teeth and lymphocytes in an area of destroyed and necrotic connective
with a periodontal abscess found during PeM were extracted.9 tissue; and a destroyed and ulcerated pocket epithelium.
The main reason for tooth extraction of teeth with a question‐
able prognosis, which had been followed‐up for 8.8 years, was the
1.3 | Etiology: risk factors
presence of periodontal abscess.11
c. Severe systemic consequences PA may develop in a pre‐existing periodontal pocket (e.g., in patients
PA may be associated with systemic dissemination of a localized with periodontitis) or in the absence of a pre‐existing periodontal
infection. Numerous case reports and series have described the pocket.
occurrence of systemic infections resulting from a suspected
source in a periodontal abscess, either through dissemination
1.3.1 | Periodontal abscess in periodontitis patients
occurring during therapy or related to an untreated abscess (see
Appendix 3, Table A3.2, in online journal). In periodontitis patients, a PA could represent a period of disease ex‐
acerbation, favored by the existence of tortuous pockets, presence of
furcation involvement16 or a vertical defect,16,17 in which the marginal
closure of the pocket could lead to an extension of the infection into
1.2 | Etiology: pathophysiology, microbiology and
the surrounding periodontal tissues.15,18,19 In addition, changes in the
histological features
composition of the subgingival microbiota, with an increase in bacterial
virulence, or a decrease in the host defense, could also result in an inef‐
1.2.1 | Pathophysiology
ficient capacity to drain the increased suppuration. Different subgroups
The first step in the development of a PA is bacterial invasion of the could be distinguished (see Appendix 3, Table A3.7, in online journal):
soft tissues surrounding the periodontal pocket, which will develop
into an inflammatory process through the chemotactic factors re‐ • Acute exacerbation:
leased by bacteria that attract polymorphonuclear leukocytes (PMN) ○ In untreated periodontitis. 20
and other cells. This will trigger intensive release of cytokines; lead ○ In “refractory” periodontitis. 21
to destruction of the connective tissues; encapsulation of the bacte‐ ○ In PeM, as previously described.
rial infection and the production of pus. Once the abscess is formed, • After different treatments:
the rate of destruction within the abscess will depend on the growth
of bacteria inside the foci; their virulence, and the local pH (an acidic ○ Scaling and root planing or professional prophylaxis: dislodged
15
environment will favor the activity of lysosomal enzymes). calculus fragments could be pushed into the tissues,20 or inade‐
quate scaling could allow calculus to remain in deep pocket areas,
whereas the coronal part would occlude the normal drainage.10
1.2.2 | Microbiology
○ Surgical periodontal therapy: associated with the presence
In general, microbiological reports on PA have shown a microbial of foreign bodies such as membranes for regeneration or
composition similar to that observed in periodontitis (see Appendix sutures. 22
3, Table A3.3, in online journal). The most prevalent bacterial ○ Systemic antimicrobial intake, without subgingival debride‐
species identified in PA, by means of different techniques (see ment, in patients with severe periodontitis could also cause
Appendix 3, Table A3.4, in online journal) were Porphyromonas gin‐ abscess formation, 23‒25 probably related to an overgrowth of
givalis (50‐100%), Prevotella intermedia, Prevotella melaninogenica, opportunistic bacteria. 23
Fusobacterium nucleatum, Tannerella forsythia, Treponema species, ○ Use of other drugs: e.g., nifedipine. 26
Campylobacter species, Capnocytophaga species, Aggregatibacter ac‐
tinomycetemcomitans or gram‐negative enteric rods (see Appendix
1.3.2 | Periodontal abscess in non‐
3, Table A3.5, in online journal). Up to now, there has been limited
periodontitis patients
evidence available on the role of viruses, the genetic characteristics
of different strains (e.g. P. gingivalis), or the antimicrobial susceptibil‐ PA can also occur in previously healthy sites, because of (see
ity of strains isolated from these lesions (see Appendix 3, Table A3.6, Appendix 3, Tables A3.8 and A3.9, in on line journal):
in online journal).
• Impaction of foreign bodies: dental floss, orthodontic elastic,
toothpick, rubber dam, or popcorn hulls.
1.2.3 | Histopathology
• Harmful habits (biting wire, nail biting, clenching) could favor ab‐
The histopathology of periodontal abscess lesions was reported as scess formation because of subgingival impaction of foreign bod‐
follows,15 after observing the lesion from the outside to the inside: a ies or to coronal closure of the pocket.
• Orthodontic factors, such as inadequate orthodontic forces or a • Self‐inflicted gingival injuries.

cross‐bite, have been reported to favor PA development. • Sickle cell anemia.
• Gingival enlargement. 27 • Abscesses after surgical procedures.
• Alterations of the root surface, including:
○ Severe anatomic alterations, such as invaginated tooth, dens

1.5 | Proposed changes to the current 1999
evaginatus (grooves) or odontodysplasia.
classification
○ Minor anatomic alterations, such as cemental tears, enamel
pearls or developmental grooves. The 1999 classification for abscesses in the periodontium included
○ Iatrogenic conditions, such as perforations. gingival, periodontal, pericoronal, and periapical abscesses.5 Relevant
○ Severe root damage: vertical root fracture or cracked tooth problems associated with this classification system included: (1) the
syndrome extending through the root. differentiation between gingival and PA, which could be confusing,
○ External root resorption. because this differentiation was simultaneously based on location
and etiology; (2) considering a PA as chronic or acute may not be ad‐
equate, because an abscess, by definition, is an acute lesion; and (3)
1.4 | Assessment and diagnosis
the inclusion of pericoronitis and periapical abscesses in the classifica‐
Data from studies with a relevant number of cases and a comprehen‐ tion together with PA might not be appropriate. Pericoronal abscesses
sive description were analyzed (Tables 1A and 1B).13,28‒31 were included in the 1999 classification, but no solid scientific basis
A series of symptoms have been reported by patients suffering for this was found in the article associated with the topic.5 In addi‐
from a PA, such as pain, tenderness of the gingiva, swelling, or tooth tion, the terms “pericoronal abscess” or “pericoronitis abscess” were
“elevation.” The most prominent sign during the oral examination was seldom used in the scientific literature; in the present literature search,
the presence of an ovoid elevation in the gingiva along the lateral part none of the articles retrieved described a pericoronal abscess as a PA.
of the root. Suppuration on probing or sampling was a common finding PAs should be classified based on their etiology (see section 3.3 and
(66–93%), whereas a fistula was not. A PA was usually associated with Table 2).
a deep periodontal pocket (7.3–9.3 mm), bleeding on probing (100%),
and increased tooth mobility (56.4–100%). Bone loss was normally
2 | N EC ROTIZ I N G PE R I O D O NTA L
observed in the radiographic examination. Extraoral findings were un‐
DISEASES
common, but could include facial swelling (3.6%), elevated body tem‐
perature, malaise, regional lymphadenopathy (7–40%) or increased
blood leukocytes (31.6%). Most abscesses affected periodontitis
patients (96.3–100%), either untreated (7.14–81.6%), in PeM (11.6– In the 1999 classification, necrotizing ulcerative gingivitis (NUG)
60%) or those undergoing active therapy (6.6–42.9%). Some studies and necrotizing ulcerative periodontitis (NUP) were included among
found molars more frequently affected,13,30 whereas others found NDPs.33 Studies have suggested that they may represent different
28 31
equal distribution, or predominance in anterior teeth. One study stages of the same disease, because they have similar etiology, clini‐
reported a higher number of abscesses at the interproximal level,13 cal characteristics, and treatment, and may even progress to more
whereas others observed more frequent abscess formation at buccal severe forms such as necrotizing stomatitis (NS) and noma.34,35 The
sites.28,30 terminology “ulcerative” was later eliminated, because ulceration
Patient history may also provide relevant information, especially was considered to be secondary to the necrosis.36
in cases of abscesses associated with previous treatments (scaling NPD patients are frequently susceptible to future recurrence of
and root planing, periodontal surgery, intake of systemic antimicro‐ disease37,38 and NPD could also become a “chronic condition,” with
bials agents, or other drugs [e.g., nifedipine] and endodontic treat‐ a slower rate of destruction.39 In cases of severe systemic involve‐
ment), or in abscesses related to foreign body impaction. ment, progression of NPD into other oral lesions could occur.40,41
Differential diagnosis (see Appendix 3, Table A3.10, in online Prevalence/incidence of NG has been reported for the overall
journal) is critical, because PA may be like other oral conditions: population or for specific groups of individuals (for references, see
Appendix 4, Tables A4.1a‐e, in online journal). In general populations
• Other odontogenic abscesses (dento‐alveolar abscesses, peri‐ attending dental clinics, the prevalence of NG ranged from 0.51 to
coronitis, endo‐periodontal abscess), or other acute conditions 3.3%; in military personnel, the prevalence and incidence reported was
(lateral periapical cyst and postoperative infection).32 higher close to the end of the 2nd World War (3.96–20.6%) than it was
• Tumor lesions, including metastatic tumoral lesions, odontogenic in more recent studies (0.19–6.19%). In African populations, highly vari‐
myxoma, non‐Hodgkin´s lymphoma, squamous cell carcinoma, able results have been reported. In students, prevalence ranged from
metastatic carcinoma. 0.9 to 6.7%. And in HIV/AIDS patients data showed wide variations:
• Other oral lesions: pyogenic granuloma, osteomyelitis, odonto‐ children (2.2‐5.0%), HIV adults (0.0–27.7% for NG and 0.3–9.0% for
genic keratocyst, eosinophilic granuloma. NP), and HIV/AIDS patients (10.1–11.1% for NG and 0.3–9.0% for NP).
TA B L E 1 A Diagnosis of periodontal abscesses: studies with series of more than 10 abscesses with comprehensive clinical description
S82
|
Study Patient sample Periodontal status Abscesses Etiology Location
Perio
Reference Country Study design n Age % female MS Initial Healthy n Name Untreated PeM treatment Trauma Teeth affected Sites affected
Smith UK Prospective‐3y 55 10‐68 50.9% 62 acute lateral 60.0% 36.4% LM (27.6%), UM interdental
PA (25.8%) (62.9%)
Hafstrom Sweden Prospective‐6 m 20 24‐79 55.0% 20 PA (clear
periodontal
origin)
Herrera Spain RCT‐30d 29 26‐65 58.6% 93.1% 6.9% 0.0% 29 PA 62.0% 24.0% 14.0% 69% M (equal buccal (48%),
U‐L) interdental
(38%), lingual
(14%)
Jaramillo Colombia Cross‐sectional 54 48.3 53.7% 87% ChP, 9.3% 3.7% 60 PA 81.6% 11.6% 6.6% 5.0% Lant (41.6%),
AgP Uant (20%)
Chan India Cross‐sectional 14 39.6 50.0% 14 PA 7.1% 50.0% 42.9% 86% U; equal buccal (71%),
M.PM.ant lingual (29%)
RCT, randomized clinical trial; y, year; m, month; d, day; p, patient; MS, moderate‐severe
L, lower jaw; U, upper jaw; M, molar; ant, anteriors; PM, premolars; PeM, periodontal maintenance; ChP, chronic periodontitis; AgP,
aggressive periodontitis
TA B L E 1 B Diagnosis of periodontal abscesses: signs and symptoms
Symptoms Signs X‐ray Extraoral Variety
Mean %PPD > Increased

Reference Pain Redness Swelling PPD 6 mm BOP SUP mobility Bone loss Fever Lymph‐adenophaty Other findings
Smith usual usual 54.8% 56.4% > 0 most, also furcation in most 0.0% 40.0% abscess pointing (69.6%), no
molars fistula, facial swelling (3.6%)
Hafstrom 100% 100% 100% 8.1 100% 68% none none tenderness (100%)
Herrera 62%MS; 75%MS 93%MS 7.3 (3‐13) 62.1% 100% 66% 79% 10.0% elevated leukocytes (31.6%)
10%none
Jaramillo 68.3% 93.3% 95% 9.3±2.5 100% 93.3% 100% 93.3%MS tooth elevation (23.3%)
Chan 7.4±1.6 71% 36.9±0.5, 7.1%
most
afebrile
PPD, probing pocket depth; freq., frequency; BOP; bleeding on probing; SUP, suppuration on probing or sampling; MS, moderate‐severe
HERRERA et al.
TA B L E 2 Proposal of classification for periodontal abscess, based on the etiological factors involved
reported very heterogeneous results, as explained in Appendix 4,

2.2 | Etiology and risk factors
Tables A4.4 in online journal.
NPD are infectious conditions; however, predisposing factors, in‐ c. Predisposing factors
cluding a compromised host immune response, are critical in the The most relevant predisposing factors for NPD were shown to
pathogenesis. be those altering the host immune response and usually more
than one factor was necessary to cause onset of the disease.49
a. Microbiology (see Appendix 4, Tables A4.2, in online journal)
The bacterial etiology of NPD, with the presence of spirochetes
2.2.1 | Human immunodeficiency virus
and fusiform bacteria, was previously demonstrated by Plaut in
infection and acquired immune deficiency syndrome
1894, and Vincent in 1896 (as reviewed in35). Furthermore, clinical
(HIV/AIDS)
improvements observed after mechanical debridement and antimi‐
crobial treatment further supported the bacterial etiology of these NPD in HIV patients may be more frequent and show faster progres‐
42
conditions. Earlier studies, using electron microscopy, suggested sion, with a higher risk of evolving into more severe lesions (NP and
tissue invasion by spirochetes.43,44 Culture studies identified P. in‐ NS), and a higher tendency for disease recurrence and poor response
termedia, and Treponema, Selenomonas and Fusobacterium species, to therapy (see Appendix 4, Tables A4.3, in online journal).
which were considered “constant flora” in NPD lesions.45 The role
of spirochetes was confirmed by immuno assays46,47 and PCR tar‐
2.2.2 | Other systemic conditions
geting 16s rRNA.48 Recent studies by phylogenetic analysis also
suggested a role of the P. intermedia and Peptostreptococcus genus Different reports have found NPD lesions associated with, or because
in the etiology of NPD. of different systemic conditions (see Appendix 4, Tables A4.5, in online
The microbiota associated with NPD in HIV (see Appendix 4, journal), or mimicking NPD, in which the lesions were part of the sys‐
Tables A4.3, in online journal) was like that of periodontitis in temic pathology (see Appendix 4, Table A4.6, in online journal).
non‐HIV patients, with some specific features, such presence and
invasion of Candida albicans, herpes viruses or superinfecting bac‐
2.2.3 | Malnutrition
terial species.
b. Host immune response Malnutrition (see Appendix 4, Tables A4.5, in online journal) could
Although the importance of host immune response in the etio‐ also be an important predisposing factor for NPD,50 especially in
pathogenesis of NPD was indisputable, the studies available developing countries.51‒53 A marked reduction in key antioxidant
nutrients and an altered acute phase response against infection

2.2.9 | Other factors
(“protein energy malnutrition”)54,55 have been reported. Other con‐
sequences were an inverse proportion in the ratio of helper and Local factors (see Appendix 4, Table A4.5d, in online journal), in‐
suppressor T‐lymphocytes, histaminemia, increased free cortisol in cluding decorative crowns71 or orthodontic therapy72 may favor the
blood and saliva, and defects in mucosal integrity. 54,56
onset of NG. Body geometry,73 thermoregulatory abnormalities,74
allelic variants for complement factors, and properdin factor B 75 or
erythrocyte catalase activity,76 have also been studied with incon‐
2.2.4 | Psychological stress and insufficient sleep
clusive results.
Certain situations of acute psychological stress or stressing situations,
and some personality traits or the ability to cope with a stressful situ‐
2.3 | Pathophysiology and histological features
ation (see Appendix 4, Tables A4.5, in online journal) may predispose
individuals to NPD. During stress periods, the immune response is NG lesions observed with light microscopy44 showed the presence
altered and the subject's behavior is changed. The biological plau‐ of an ulcer within the stratified squamous epithelium and the super‐
sibility of this assumption is based on the reduction of gingival mi‐ ficial layer of the gingival connective tissue, surrounded by a nonspe‐
crocirculation and salivary flow; increase in serum and urine levels cific acute inflammatory reaction. Four regions have been described:
of 17‐hydroxycorticosteroid (17‐OHCS)57; change in the function of the (1) superficial bacterial area; (2) neutrophil‐rich zone; (3) necrotic
PMN and lymphocytes, and increase in periodontal pathogen levels zone; (4) spirochetal infiltration zone. Additional findings included
45
(P. intermedia). plasma cells in the deeper parts and IgG and C3 between epithelial
cells.77 These observations have been confirmed by electron micros‐
copy, adding areas of transition to a chronic stage of inflammation.43
2.2.5 | Inadequate oral hygiene, pre‐existing
gingivitis, and previous history of NPD
Plaque accumulation has been considered a predisposing factor for
NPD, which may also be aggravated by limited tooth brushing be‐ Diagnosis of NPD should be primarily based on clinical findings.35,78
37,58,59
cause of pain. NPD usually occurred secondarily to a previ‐ Microbiological or biopsy assessment may be recommended in cases
39,60
ously existing periodontal disease (chronic gingivitis, previous of atypical presentations or nonresponding cases.
NPD58) (see Appendix 4, Tables A4.5, in online journal). The most relevant clinical findings in NG (Table 3) reported in
relevant studies (with 35 or more patients58,64,67,70) were: necrosis
and ulcer in the interdental papilla (94–100%), gingival bleeding (95–
2.2.6 | Tobacco and alcohol consumption
100%), pain (86–100%), pseudomembrane formation (73–88%), and
Most adult patients with NPD are smokers.39,61‒65 Alcohol consumption halitosis (84–97%). Extraoral signs included adenopathy (44–61%) or
has also been associated with the physiological and psychological fac‐ fever (20‐39%). In children,52 pain and halitosis were less frequent,
58,66
tors favoring NPD (see Appendix 4, Tables A4.5, in online journal). whereas fever, adenopathy, and sialorrhea were more frequent.
For NP,79 in addition to the previous signs and symptoms, peri‐
odontal attachment and bone destruction were observed, together
2.2.7 | Young age and ethnicity
with more frequent extraoral signs. In severely immune‐compro‐
Young people (15‐34 years old) in the developed world are at a mised patients, bone sequestrum could occur.80 NP could be the
higher risk of suffering from NPD, frequently in combination with result of one or various episodes of NG (less frequent pocket forma‐
other predisposing factors.58,64,67,68 Children are at a higher risk in tion), or of NG occurring at a site previously affected by periodontitis
developing countries, and this is normally associated with malnu‐ (periodontal pocketing would be found).34,81
52,53,56,69
trition and other infections. Some studies suggested that In NS, bone denudation extended through the alveolar mu‐
58,64,70
Caucasians suffered from NPD more frequently than other cosa, with larger areas of osteitis and bone sequestrum, in severely
ethnic groups, however, this finding needs to be confirmed (see compromised systemic patients (HIV/AIDS patients, severe malnu‐
Appendix 4, Tables A4.5, in online journal). trition). Atypical cases have also been reported, in which NS devel‐
oped without the appearance of previous NPD lesions. 82‒85
Clinical criteria for identifying NG, NP, NS and Noma, accord‐
2.2.8 | Seasonal variations
ing to the studies included in the present review, are summarized in
Different studies (see Appendix 4, Table A4.5e in online journal) Appendix 4, Tables A4.7,8,9, in online journal.
have evaluated the hypothesis of the effect of seasonal variations
on the prevalence of NPD: in central Africa, NPD peaked in the rainy
2.4.1 | Differential diagnosis
season; less clear patterns were observed in military personnel, stu‐
dents or general populations, although winter months were normally It is mandatory to establish a differential diagnosis with vesicular‐bul‐
peak periods, except in South Africa. lous diseases, primary or recurrent herpetic gingivostomatitis,86,87 oral
HERRERA et al.
TA B L E 3 Diagnosis of necrotizing periodontal diseases: frequent clinical findings
Primary symptoms and signs Other symptoms and signs
Pseudo‐mem‐
Patients, Gingival Gingival branous
Reference Country Study design Population condition necrosis bleeding Pain formation Halitosis Adenopathies Fever Other features
Barnes USA Case‐control Military 218 ANUG 94.0% 95.5% 86.2% 73.4% 84.4% na No Cratering (79.8%);
frequent wooden or
wedge‐like
(40.4%); bad
taste (39.4%)
Stevens USA Epidemiological General 51 ANUG 100% 100% 100% na na na 20% na
(1y) and case and population
control
Falkler USA Case and control Clinic at urban 35 ANUG 100% 100% 100% 85% 97% 61% 39% na
dental school
Horning USA 5y epidemiological Military (10 68 NG 100% 100% 100% 88% 87% 44% 24% Interdental
study HIV) gingival craters
(previous NG)
(21%)
Jimenez Colombia Prospective case Children 28 NUG, 9 100% 96.43% 53.57% Acute cases 50% Submaxilar 67.9% Tooth mobility
series Noma (57.1%), (46.43%);
Submaxilar & sialorrhea
cervical (42.86%)
(21.4%)
Cobb USA Case series HIV 16 NUP 100% 100% 100% 81.3% 100% 68.8% 43.8% Advanced
generalized
alveolar bone
loss (100%)
y, years; na, not available; HIV, human immunodeficiency virus; ANUG, acute necrotizing ulcerative gingivitis; NUG, necrotizing ulcerative gingivitis;
NG, necrotizing gingivitis; NUP, necrotizing ulcerative periodontitis
|
S85
TA B L E 4 Proposal of classification for necrotizing periodontal diseases (NPD)
NG, necrotizing gingivitis; NP, necrotizing periodontitis; NS, necrotizing stomatitis

a
Mean plasma and serum concentrations of retinol, total ascorbic acid, zinc, and albumin markedly reduced, or very marked depletion of plasma retinol,
zinc, and ascorbate; and saliva levels of albumin and cortisol, as well as plasma cortisol concentrations, significantly increased
b
Living in substandard accommodations, exposure to debilitating childhood diseases, living near livestock, poor oral hygiene, limited access to potable
water and poor sanitary disposal of human and animal fecal waste
c
Measles, herpes viruses (cytomegalovirus, Epstein‐Barr virus‐1, herpes simplex virus) chicken pox, malaria, febrile illness
manifestation mimicking NPD lesions (see Appendix 4, Table A4.6, in 3 | E N D O ‐ PE R I O D O NTA L LE S I O N S

88
online journal) and toothbrush abrasion.
2.5 | Proposed changes to the current 1999 EPL are clinical conditions involving both the pulp and periodontal tis‐
classification sues and may occur in acute or chronic forms. When they are associ‐
ated with a recent traumatic or iatrogenic event (e.g. root fracture or
In the present 1999 classification, the consensus report established
perforation), the most common manifestation is an abscess accompa‐
“that necrotizing ulcerative gingivitis and necrotizing ulcerative peri‐
nied by pain. However, EPL, in subjects with periodontitis, normally
odontitis should be collectively referred to as Necrotizing Periodontal
present slow and chronic progression without evident symptoms.
Diseases.” The group agreed that both diseases were associated with a
The most common signs and symptoms associated with a tooth
diminished systemic resistance to bacterial infection. This rather sim‐
affected by an EPL are deep periodontal pockets reaching or close to
plistic approach did not consider the huge differences in prevalence,
the apex and negative or altered response to pulp vitality tests. The
risk of progression, and extent and severity of NPD among patients
other signs and symptoms reported, in order of prevalence, are: bone
with different predisposing conditions. NPD in HIV/AIDS patients or in
resorption in the apical or furcation region, spontaneous pain or pain
malnourished children in developing countries may represent a severe
on palpation and percussion, purulent exudate, tooth mobility, sinus
and even life‐threating condition (in the latter case). Conversely, NPD
tract, crown, and gingival color alterations (Table 5).
in smokers and stress adult patients in developed countries repre‐
sented a relevant but normally non‐threatening condition. Therefore,
patients continuously exposed to a severe systemic compromise (see 3.2 | Etiology and risk factors
previous examples) have a higher risk of suffering from NPD and of
3.2.1 | Primary etiology
faster and more severe progression (from NG to NP, and even to NS
and Noma). Conversely, in patients with a systemic compromise of lim‐ An established EPL is always associated with varying degrees of mi‐
ited duration (e.g. stressful situation in students or militaries), NG may crobial contamination of the dental pulp and the supporting peri‐
not progress, although the lesions would be different if they affected a odontal tissues. Nonetheless, the primary etiology of these lesions
gingivitis or a periodontitis patient. A proposal for a new classification might be associated with (1) endodontic and/or periodontal infec‐
system is presented in Table 4. tions or (2) trauma and/or iatrogenic factors.
TA B L E 5 Main characteristic of the studies included in the endo‐periodontal lesion review, stratified by the periodontal condition
HERRERA et al.
Percentage (%) of studies

according to each study design
Signs Signs and symptoms
Deep
periodontal Gingival
Periodontal Study Number of pocket Altered pulp Purulent Apical bone Sinus Tooth color Crow color
condition design References teeth included (≥5 mm) response exudate resorption tract mobility alteration alteration Pain
Periodontitis CR Aksel; Blanchard 5 100 100 50 100 50 50 0 0 100

patients
CS Didilescu; Fatemi; Gomes; 190 100 100 0 75 0 12.5 0 0 25
Kipioti ; Kobayashi; Rupf;
Pereira; Li
RCT Cortellini ; Gupta 62 100 100 0 0 0 0 0 0 0
TOTAL 257 100 100 8.3 83.3 8.3 16.6 0 0 33.3
Nonperiodontitis CR Asgary; Attam; Ballal; 39 100 100 33.3 70.3 33.3 29.6 3.7 7.4 55.5
patients Castelo‐Baz; Coraini;
Floratos; Fujii; Gandhi;
Goyal; Haueisen; Jivoinovici;
Kambale; Karabucak; Keceli;
Kerezoudis; Kishan; Koyess;
Mali; Miao; Nagaveni; Oh;
Oh; Pickel; Sharma; Singh;
Sooratgar; White
CS Xia 13 100 100 0 100 0 0 0 0 0
TOTAL 52 100 100 32.1 71.4 32.1 28.5 3.5 7.1 53.5
Unclear CR Karunakar; Narang; Solomon; 8 100 100 83.3 100 33.3 66.6 0 0 50
Tobón‐Arroyave; Tseng;
Varughese
CrS Rhee 168 100 100 0 100 0 0 0 0 0
CS Li; Nicopoulou‐Karayianni; 69 100 100 0 100 0 0 0 0 0
Pereira
TOTAL 245 100 100 50 100 20 40 0 0 30
FINAL TOTAL Number of studies: 50 554 100 100 30 80 24 28 5 4 44
CR: Case report; CS: Clinical study; RCT: Randomized clinical trial; CrS: Cross‐sectional
|
S87
Endo‐periodontal lesions associated with endodontic and

3.2.3 | Risk factors
periodontal infections
They might be triggered: (1) by a carious lesion that affects the pulp The main risk factors for the occurrence of EPL were advanced peri‐
and, secondarily, affects the periodontium; (2) by periodontal de‐ odontitis, trauma, and iatrogenic events. Other reported risk factors
struction that secondarily affects the root canal; (3) or by both events were the presence of grooves, furcation involvement, porcelain‐fused‐
concomitantly. The latter type occurs less frequently and is usually re‐ to‐metal crowns and active carious lesions (see Appendix 5, Table
ferred to as a “true‐combined” or “combined” lesion.89,90 These lesions A5.1, in online journal). Furcation involvement, high level of bone de‐
may develop in subjects with periodontal health91‒93 or disease94,95 struction around the affected tooth, and anatomic problems (e.g. the
(Table 6). The periodontal condition has an important impact in the presence of grooves), could worsen the prognosis of EPL. Most of the
prognosis of the EPL because of the striking changes in the oral ecol‐ single EPL in non‐periodontitis patients reported in the literature were
ogy of subjects with periodontal diseases. Converting this ecology associated with palatal grooves.
back into a healthy state is challenging,96,97 especially in patients with
severe periodontitis and in teeth with deep pockets, as in the case of
3.3 | Pathophysiology and histological features
EPL. Therefore, a detailed periodontal examination is a very important
step for the accurate diagnosis and treatment plan of EPL. The dental pulp and the periodontium have different communica‐
tion pathways, such as the apical radicular foramina, accessory (or
Endo‐periodontal lesions associated with trauma and lateral) canals, and dentinal tubules.112 Accessory canals are more
iatrogenic factors prevalent at the apical third of the roots, but they may be found in
These conditions usually have a poor prognosis as they affect the tooth high numbers in other areas, such as in the furcation regions.112,113
structure. The most common lesions in this category were: (1) root/pulp Pathological communication between these structures, which in‐
chamber/furcation perforation (e.g. because of root canal instrumenta‐ cludes the migration of microorganisms and inflammatory media‐
98
tion or to tooth preparation for post‐retained restorations) ; (2) root tors between the root canal and the periodontium, may lead to the
fracture or cracking (e.g., because of trauma or tooth preparation for EPL.89,112‒116
98
post‐retained restorations) ; (iii) external root resorption (e.g., because of
trauma)99; or (iv) pulp necrosis (e.g., because of trauma) draining through
the periodontium100 (see Appendix 5, Table A5.1, in online journal).
The classification system most commonly used for the diagnosis of EPL
was published in 1972 by Simon et al.89 and included the following
3.2.2 | Microbiology
categories: (1) primary endodontic lesions; (2) primary endodontic le‐
Only a few studies to date have evaluated the microbiota of EPL sions with secondary periodontal involvement; (3) primary periodontal
using culture,101‒103 “targeted” molecular techniques (polymerase lesions; (4) primary periodontal lesions with secondary endodontic in‐
chain reaction [PCR]90,94,103,104 real time PCR105 and checkerboard volvement; and (5) “true” combined lesions. The main drawback of this
DNA‐DNA hybridization90), or “open‐ended” molecular techniques classification and a recent proposed amendment117 was to base their
(Next Generation Sequencing [NGS]95 and Denaturing Gradient categories on the primary source of infection (root canal or periodon‐
Gel Electrophoresis [DGGE] or cloning and sequencing94,104) (see tal pocket). This seemed to be a suitable approach, as lesions of peri‐
Appendix 5, Table A5.2, in online journal). Overall, these studies odontal origin might have a worse prognosis than those of endodontic
showed a great similarity between the microbiota found in the root ca‐ origin. Nonetheless, using “history of the disease” as the main criteria
nals and periodontal pockets. Most of the bacterial species identified for diagnosis was not practical, because in the majority of cases the
were recognized periodontal pathogens from the so called “red” and complete history is unavailable to the clinician. In addition, determin‐
“orange” complexes,106 such as P. gingivalis, T. forsythia, or Parvimonas ing the primary source of infection is not relevant for the treatment of
micra, and species from the genera Fusobacterium, Prevotella and Tr EPL, as both the root canal and the periodontal tissues would require
eponema. 90,103,105,107‒109
Studies using “open‐ended” molecular tech‐ treatment.118,119 Thus, ideally, the diagnosis and classification of EPL
94,95,104
niques observed a higher microbial diversity and identified less should be based on the present disease status and on the prognosis of
common taxa, such as Filifactor alocis, Enterococcus faecalis, and spe‐ the tooth involved, which would determine the first step of the treat‐
cies from the genera Desulfobulbus, Dialister, Fretibacterium, or Rothia. ment planning that would be whether to maintain or extract the tooth.
Incidentally, most of these species and genera have recently also been The three main prognostic groups for a tooth with an EPL are:
associated with chronic or aggressive periodontitis.110,111 (1) hopeless, (2) poor, and (3) favorable. The hopeless prognosis is
Taken together, the above‐mentioned data suggest that there normally associated with EPL caused by trauma or iatrogenic fac‐
are no major differences between the microorganisms found in the tors, whereas the prognosis of a tooth with an EPL associated with
endodontic and periodontal lesions, or a specific microbial profile endodontic and periodontal infections may range from favorable to
associated with the EPL. This was somehow expected, as both sites hopeless, depending on the extension of the periodontal destruction
of infection (root canal and periodontal pockets) are anaerobic envi‐ around the affected tooth, and the presence and severity of the peri‐
ronments exposed to similar nutrients. odontal disease affecting the patient's oral health.
TA B L E 6 Proposal for endo‐periodontal lesions classification
The first steps in diagnosis should be to assess patient's history discriminative to help the clinician to determine the most effective
and clinical or radiographic examination. Patient history is import‐ treatment for a particular lesion. Finally, EPL should be classified ac‐
ant for identifying the occurrence of trauma, endodontic instru‐ cording to signs and symptoms feasible to be assessed at the time that
mentation or post preparation. If one or more of these events are the lesion is detected and that have direct impact on their treatment,
identified, detailed clinical and radiographic examinations should such as presence or absence of fractures and perforations, presence or
be conducted to seek the presence of perforations, fractures, and absence of periodontitis, and the extent of the periodontal destruction
cracking or external root resorption. Careful radiographic evaluation around the affected teeth (Table 6).
and clinical examination of the root anatomy is of great importance
at this stage, to assess the integrity of the root and to help with dif‐
ferential diagnosis. A radicular groove, for example, might mimic a O B S E RVATI O N S A N D D I S CU S S I O N
120
vertical root fracture in the radiograph.
If perforations and fractures are not identified, the diagnosis should The present literature review focused on three conditions that have
proceed to a second phase consisting of full‐mouth periodontal assess‐ in common a possible acute onset and severe destruction. A com‐
ment, including probing depth, attachment level, bleeding on probing, prehensive analysis of the available scientific literature (336 studies
suppuration and mobility, as well as tooth vitality and percussion tests. were included) allowed for a description of the importance, etiol‐
The presence of a periodontal pocket reaching or close to the apex com‐ ogy, pathogenesis and diagnosis, together with the proposal of new
bined with absence of pulp vitality would indicate the presence of an EPL. classifications.
3.5 | Proposed changes to the current 1999 Quality of the available evidence
classification
In general, the evidence to define the etiology, diagnosis, prognosis and
For the first time, the 1999 classification system for Periodontal treatment of the teeth affected by the three conditions studied was
118,121
Diseases and Conditions included the EPLs, which were de‐ considered limited. Most of the included studies were case reports with
scribed under Section VII ‐ Periodontitis Associated with Endodontic small sample sizes. Very few clinical studies with a reasonable number
Lesion, as a single category entitled “Combined Periodontal‐ of cases were found, and no robust epidemiological studies were iden‐
Endodontic Lesions.” An advantage of this classification over the previ‐ tified (see Appendix 1 in online journal). To enable solid evidence on
89,117
ous ones was that it reflected the current clinical condition of the these lesions to be made available, additional studies with adequate
lesion, thereby overcoming the problem of using “history of the dis‐ designs and sample sizes are needed, specifically on the topics with less
ease” as the main criteria. Nonetheless, the following problems were information available (e.g. PA in non‐periodontitis patients, and EPL).
associated with this classification system: (1) grouping all EPL under
a single section entitled “Periodontitis Associated with Endodontic
Pending topics for the proposed classification
Lesion” was not ideal, as these lesions may occur in subjects with or
without periodontitis; (2) the single category presented, “Combined The topic of whether the lesions associated with root alterations and
Periodontal‐Endodontic Lesions”, was too generic and not sufficiently damage (e.g. fracture, perforation, root resorption), should be classified
in a different category, is debatable. However, because these lesions 3. Herrera D, Alonso B, de Arriba L, Santa Cruz I, Serrano C, Sanz M.
are EPL in nature (i.e., invariably affect both the periodontium and the Acute periodontal lesions. Periodontol 2000. 2014;65:149–177.
4. Rotstein I, Simon JH. Diagnosis, prognosis and decision‐making
pulp‐root canal complex, irrespective of being associated with abscess
in the treatment of combined periodontal‐endodontic lesions.
formation, or not), we understand that they should be classified as such. Periodontol 2000. 2004;34:165–203.
Thus, in the classification system suggested for EPL, these conditions 5. Meng HX. Periodontal abscess. Ann Periodontol. 1999;4:79–83.
are grouped as “EPL associated with trauma and iatrogenic factors.” 6. Gill Y, Scully C. Orofacial odontogenic infections: review of mi‐
crobiology and current treatment. Oral Surg Oral Med Oral Pathol.
Pericoronal abscesses have been excluded from the category of
1990;70:155–158.
PA.121 However, pericoronitis may still be considered an acute peri‐ 7. van Winkelhoff AJ, Carlee AW, de Graaff J. Bacteroides endodonta‐
odontal condition, but in a separate category. lis and other black‐pigmented Bacteroides species in odontogenic
“Periodontal” abscesses around implant sites have also been de‐ abscesses. Infect Immun. 1985;49:494–497.
8. Gray JL, Flanary DB, Newell DH. The prevalence of periodontal
scribed.122,123 Considering that from a histological point of view the
abscess. J Indiana Dent Assoc. 1994;18‐20:22–13. 73. quiz 24.
lesions may be similar, it is also debatable whether they should be 9. McLeod DE, Lainson PA, Spivey JD. Tooth loss due to periodontal
given a different name should be given to these lesions (e.g. “periim‐ abscess: a retrospective study. J Periodontol. 1997;68:963–966.
plant” abscesses) and whether they should be classified together 10. Kaldahl WB, Kalkwarf KL, Patil KD, Molvar MP, Dyer JK. Long‐
term evaluation of periodontal therapy: i. Response to 4 therapeu‐
with the other abscesses in the periodontium.
tic modalities. J Periodontol. 1996;67:93–102.
In this manuscript, the term “risk factor” was used, however, in
11. Chace R, Sr, Low SB. Survival characteristics of periodon‐
some cases, the available literature was insufficient to support the tally‐involved teeth: a 40‐year study. J Periodontol. 1993;64:
use of this term. 701–705.
12. Silva GL, Soares RV, Zenobio EG. Periodontal abscess during sup‐
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Received: 9 December 2017 | Revised: 11 March 2018 | Accepted: 12 March 2018

2017 WORLD WORKSHOP

Periodontal health and gingival diseases and conditions on

© 2018 American Academy of Periodontology and European Federation of Periodontology

S68 | wileyonlinelibrary.com/journal/jcpe J Clin Periodontol. 2018;45(Suppl 20):S68–S77.

herpes simplex, histoplasmosis, Hodgkin lymphoma, hyperglycemia, hyposalivation, intact

“Health is a state of complete physical, mental and social well‐being

Intact periodontium Health Gingivitis

Probing attachment loss No No

Probing attachment loss Yes Yes

Probing attachment loss Yes Yes

TA B L E 2 Classification of gingival health and gingival diseases/ TA B L E 2 (Continued)

TA B L E 2 (Continued) 1. Tip diameter 0.5 mm

Workshop participants filed detailed disclosure of potential conflicts

FIGURE 1 Participants of Workgroup 1

2017 WORLD WORKSHOP

Dental plaque–induced gingival conditions

Shinya Murakami1 | Brian L. Mealey2 | Angelo Mariotti3 | Iain L.C. Chapple4

© 2018 American Academy of Periodontology and European Federation of Periodontology

J Clin Periodontol. 2018;45(Suppl 20):S17–S27.  wileyonlinelibrary.com/journal/jcpe | S17

Behavioural risk factors absent Behavioural risk factors present

Environmental risk factors absent Environmental risk factors evident

TA B L E 2 Classification of plaque‐induced gingivitis and

85.5% (male) 78.8% (female)

83% including periodontitis

BOP, calculus, pocket depth,

Bleeding on gentle sweep of

the gingival margin

of plaque‐induced gingivitis can be influenced by tooth and root

probing attachment levels of individuals with plaque‐induced gin‐

givitis will generally not indicate loss of supporting structures.

gen fiber network with changes in collagen types, cytopathologic

alterations of resident fibroblasts, and a progressive inflammatory/

immune cellular infiltrate.16 Although recent studies suggest that

are needed to clearly define the microbial community of gingivi‐

tis. In this regard, gingivitis is a non‐specific dental plaque–induced

inflammatory condition, a concept that remains unchanged from

The molecular characteristics or the pattern of the gingival

Retired persons in U.S.

transcriptome (i.e., sum total of all mRNA expressed by genes

tion have been scrutinized since the last classification work‐

shop. Because mRNA transcripts are not always translated into

val inflammation, and which are risk factors or risk predictors of

gingival inflammation. Currently, several broad biologic changes

in the transcription of genes from non‐inflamed to inflamed gin‐

U.S. Public Health

U.S. Public Health

include: 1) host‐bacterial interactions, including but not limited to

microbial pattern recognition molecules; 2) host cell chemotaxis;

3) phagocytosis and degranulation; 4) novel cellular/molecular

pathway signaling, including but not limited to cytokine signaling

and cell adhesion; 6) T lymphocyte response; 7) angiogenesis; and

8) epithelial immune response. 26,27 At this time, the role of the

tion to gingival inflammation.

TA B L E 3 Summary of studies on menstrual cycle‐associated gingival changes

AC K N OW L E D G M E N T S A N D D I S C LO S U R E S 24. Shaw L, Harjunmaa U, Doyle R, et al. Distinguishing the sig‐

2017 WORLD WORKSHOP

A new classification scheme for periodontal and peri‐implant

Jack G. Caton1 | Gary Armitage2 | Tord Berglundh3 | Iain L.C. Chapple4 |

© 2018 American Academy of Periodontology and European Federation of Periodontology

S68 | wileyonlinelibrary.com/journal/jcpe J Clin Periodontol. 2018;45(Suppl 20):S68–S77.

J Clin Periodontol. 2018;45(Suppl 20):S17–S27. wileyonlinelibrary.com/journal/jcpe | S17

J Clin Periodontol. 2018;45:45(Suppl 20);S1–S8. wileyonlinelibrary.com/journal/jcpe | S1

S28 | wileyonlinelibrary.com/journal/jcpe J Clin Periodontol. 2018;45(Suppl 20):S28–S43.